Introduction of different types of primary and secondary messengers including hydrophilic, hydrophobic and gaseous.
it also describes the intracellular pathway of cyclic amp, jak stat and mapk in a very simple language.
The JAK/STAT pathway involves cytokines binding to cell surface receptors which activates JAK kinases, leading to phosphorylation of STAT transcription factors. STAT dimers then enter the nucleus and regulate transcription of genes involved in processes like proliferation, differentiation, and survival. Disregulation of the JAK/STAT pathway contributes to diseases like leukemia, and JAK inhibitors have been developed for leukemia therapy.
This document discusses second messengers, which are intracellular molecules that amplify and spread signals from receptors on the cell surface. It describes four main classes of second messengers - cyclic nucleotides, membrane lipid derivatives, calcium ions, and gases like nitric oxide. Specifically, it examines the cAMP, cGMP, IP3/DAG, and calcium-mediated signaling pathways, outlining the ligands, effectors, and downstream effects of each messenger. It also provides details on nitric oxide and calcium signaling within cells.
Assignment on Secondary messengers and intracellular signalingDeepak Kumar
Assignment on Secondary messengers: cyclic AMP, cyclic GMP, calcium ion, inositol 1,4,5- trisphosphate, (IP3), NO, and diacylglycerol. Detailed study of following intracellular signaling pathways: cyclic AMP signaling pathway, mitogen-activated protein kinase (MAPK) signaling, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway.
The document discusses the MAP kinase pathway and JAK-STAT pathway. It describes that the MAP kinase pathway involves signal transmission from activated RAS through a protein kinase cascade to MAP kinase, which then activates transcription factors in the nucleus. It also explains that the JAK-STAT pathway involves cytokine receptors activating associated JAK kinases, which phosphorylate and activate STAT proteins that dimerize and move to the nucleus to regulate gene expression. Both pathways play important roles in signal transduction and regulating gene transcription in cells.
This document summarizes the cyclic AMP pathway, which is a major intracellular signaling pathway utilized by many hormones and extracellular molecules. It involves hormones binding to cell surface receptors and activating G proteins, which then activate the enzyme adenylyl cyclase to produce the second messenger cyclic AMP (cAMP) from ATP. cAMP then activates protein kinase A and leads to phosphorylation of target proteins to elicit physiological responses. The actions of cAMP are terminated by phosphodiesterase breaking it down into AMP or by phosphatases dephosphorylating proteins. Disruption of this pathway by toxins can impair the host's defense abilities.
1. Second messengers are small intracellular molecules that transmit signals within cells after extracellular signaling molecules (hormones or neurotransmitters) bind to cell surface receptors.
2. There are three main types of second messenger systems: cyclic AMP (cAMP), cyclic GMP (cGMP), and inositol trisphosphate (IP3)/diacylglycerol (DAG). These systems activate protein kinases or trigger the release of calcium ions to produce a physiological response.
3. Second messengers amplify and diversify extracellular signals, allowing for precise regulation of multiple cellular processes. Their roles are important for understanding cell signaling, disease mechanisms, and potential drug targets.
Genetic variation in G protein coupled receptorsSachinGulia12
This document discusses genetic variation in G protein-coupled receptors (GPCRs). It notes that GPCRs are membrane proteins involved in cell signaling and the targets of many drugs. Genetic variations can influence drug efficacy and safety through several mechanisms: by altering the structure and function of GPCRs, their coupling to G proteins and signaling pathways, their binding pockets, and their spontaneous signaling. Specific examples of genetic variations in GPCRs that are associated with human diseases are also provided.
Nuclear receptors are a family of transcription factors that regulate gene expression in response to small lipophilic compounds like steroid hormones and lipids. They have a conserved structure of six domains including a ligand binding domain that activates gene expression when a ligand is present. Nuclear receptors function by binding to DNA as monomers or dimers and recruiting other proteins to regulate transcription. They are classified into three classes based on their ligand, subcellular localization, and mechanism of action.
The JAK/STAT pathway involves cytokines binding to cell surface receptors which activates JAK kinases, leading to phosphorylation of STAT transcription factors. STAT dimers then enter the nucleus and regulate transcription of genes involved in processes like proliferation, differentiation, and survival. Disregulation of the JAK/STAT pathway contributes to diseases like leukemia, and JAK inhibitors have been developed for leukemia therapy.
This document discusses second messengers, which are intracellular molecules that amplify and spread signals from receptors on the cell surface. It describes four main classes of second messengers - cyclic nucleotides, membrane lipid derivatives, calcium ions, and gases like nitric oxide. Specifically, it examines the cAMP, cGMP, IP3/DAG, and calcium-mediated signaling pathways, outlining the ligands, effectors, and downstream effects of each messenger. It also provides details on nitric oxide and calcium signaling within cells.
Assignment on Secondary messengers and intracellular signalingDeepak Kumar
Assignment on Secondary messengers: cyclic AMP, cyclic GMP, calcium ion, inositol 1,4,5- trisphosphate, (IP3), NO, and diacylglycerol. Detailed study of following intracellular signaling pathways: cyclic AMP signaling pathway, mitogen-activated protein kinase (MAPK) signaling, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway.
The document discusses the MAP kinase pathway and JAK-STAT pathway. It describes that the MAP kinase pathway involves signal transmission from activated RAS through a protein kinase cascade to MAP kinase, which then activates transcription factors in the nucleus. It also explains that the JAK-STAT pathway involves cytokine receptors activating associated JAK kinases, which phosphorylate and activate STAT proteins that dimerize and move to the nucleus to regulate gene expression. Both pathways play important roles in signal transduction and regulating gene transcription in cells.
This document summarizes the cyclic AMP pathway, which is a major intracellular signaling pathway utilized by many hormones and extracellular molecules. It involves hormones binding to cell surface receptors and activating G proteins, which then activate the enzyme adenylyl cyclase to produce the second messenger cyclic AMP (cAMP) from ATP. cAMP then activates protein kinase A and leads to phosphorylation of target proteins to elicit physiological responses. The actions of cAMP are terminated by phosphodiesterase breaking it down into AMP or by phosphatases dephosphorylating proteins. Disruption of this pathway by toxins can impair the host's defense abilities.
1. Second messengers are small intracellular molecules that transmit signals within cells after extracellular signaling molecules (hormones or neurotransmitters) bind to cell surface receptors.
2. There are three main types of second messenger systems: cyclic AMP (cAMP), cyclic GMP (cGMP), and inositol trisphosphate (IP3)/diacylglycerol (DAG). These systems activate protein kinases or trigger the release of calcium ions to produce a physiological response.
3. Second messengers amplify and diversify extracellular signals, allowing for precise regulation of multiple cellular processes. Their roles are important for understanding cell signaling, disease mechanisms, and potential drug targets.
Genetic variation in G protein coupled receptorsSachinGulia12
This document discusses genetic variation in G protein-coupled receptors (GPCRs). It notes that GPCRs are membrane proteins involved in cell signaling and the targets of many drugs. Genetic variations can influence drug efficacy and safety through several mechanisms: by altering the structure and function of GPCRs, their coupling to G proteins and signaling pathways, their binding pockets, and their spontaneous signaling. Specific examples of genetic variations in GPCRs that are associated with human diseases are also provided.
Nuclear receptors are a family of transcription factors that regulate gene expression in response to small lipophilic compounds like steroid hormones and lipids. They have a conserved structure of six domains including a ligand binding domain that activates gene expression when a ligand is present. Nuclear receptors function by binding to DNA as monomers or dimers and recruiting other proteins to regulate transcription. They are classified into three classes based on their ligand, subcellular localization, and mechanism of action.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
Applications of Genomic and Proteomic ToolsRaju Paudel
This document provides an overview of genomic and proteomic tools. It discusses topics like genomics, which is the study of genomes including structural and functional genomics. Proteomics is defined as the large-scale study of proteins, their structures and functions. Several techniques are described briefly, including DNA gel electrophoresis, polymerase chain reaction (PCR), real-time PCR, DNA sequencing, microarray technology, enzyme-linked immunosorbent assay (ELISA), and blotting techniques like Southern blotting, Northern blotting and Western blotting. Applications of these various tools are also mentioned.
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The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals).[1] Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
This document discusses cell signaling via cyclic AMP (cAMP) pathways. It begins by explaining primary and secondary messengers, with an emphasis on the role of cAMP as a secondary messenger. It then describes the steps of the cAMP pathway in detail, including the G protein-coupled receptor, activation of adenylyl cyclase and conversion of ATP to cAMP, activation of protein kinase A by cAMP, and regulation of glycogen metabolism. The document discusses mechanisms of feedback regulation of the cAMP pathway to terminate the cellular response, such as receptor desensitization and degradation of cAMP by phosphodiesterase.
This document summarizes kinase receptors and nuclear receptors. Kinase receptors contain an extracellular ligand-binding domain connected by a transmembrane helix to an intracellular domain with kinase activity. They signal through phosphorylation cascades like MAPK. Nuclear receptors regulate gene transcription as ligand-activated transcription factors. They contain a ligand binding domain, DNA binding domain, and transcriptional regulation domain. Nuclear receptors form dimers and recruit cofactors to modify gene expression.
Secondary messengers are intracellular signaling molecules that are released within cells in response to extracellular signaling molecules known as first messengers like hormones and neurotransmitters. Common examples include cyclic AMP, inositol trisphosphate, diacylglycerol, and calcium ions. These secondary messengers help amplify and propagate intracellular signals by binding to target proteins and modulating their activity, often through phosphorylation. They allow cells to mount robust physiological responses despite the extracellular signals not directly crossing the cell membrane.
Nuclear receptor type I are intracellular receptors found in the cytoplasm that respond to hydrophobic ligands. When ligands bind, the receptor-ligand complex undergoes a conformational change that exposes a DNA-binding site, allowing it to move to the nucleus and bind to specific regulatory regions of DNA to promote transcription of genes without needing to pass the signal to other proteins. Nuclear receptors can function as monomers, homodimers, or heterodimers to regulate transcription.
G Protein–Coupled Receptors (GPCRs) are integral membrane proteins that are activated by extracellular signaling molecules and activate intracellular secondary messenger pathways. They have seven transmembrane domains and activate heterotrimeric G proteins upon ligand binding. The G protein then activates downstream effector enzymes like adenylyl cyclase, which generates secondary messengers like cAMP. These messengers go on to activate pathways that ultimately alter cell function. The beta-adrenergic receptor pathway is a key example, with epinephrine binding and cAMP production leading to protein kinase A activation. PKA then phosphorylates target proteins to produce effects like increased heart rate. GPCRs are major drug targets, and their deregulation
Introduction to Genetic Variation in GPCR
G-Protein couple Receptor
Genetic variation in GPCRs
V2 Vasopressin Receptor, Thrombroxane Receptor, P2Y 12ADP Receptor, Chemokine Receptor, Biogenic amine receptors
Presented by
R. REKHA
Department of Pharmacology
This document summarizes the JAK-STAT signaling pathway. It describes that the pathway involves Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins that communicate chemical signals from outside the cell to the cell's nucleus. The JAK-STAT pathway is involved in processes like immunity, cell division, cell death, and tumor formation. Disruptions to the pathway can lead to diseases affecting the skin, immune system, and cancers. The document outlines the key steps of the pathway including cytokine binding, JAK phosphorylation, STAT phosphorylation and dimerization, STAT transport to the nucleus to act as a transcription factor.
The JAK-STAT signaling pathway transmits signals from extracellular chemicals to the nucleus, activating transcription of target genes. It consists of a cell surface receptor, associated Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When a ligand binds the receptor, JAKs phosphorylate STATs, which form dimers and translocate to the nucleus to regulate gene expression. The Ras/MAPK pathway similarly relays signals from cell surface receptors via Ras, Raf, MEK, and MAPK proteins to influence transcription. Both pathways are tightly regulated and important for processes like cell growth, differentiation, and apoptosis, with dysregulation contributing to diseases.
Classification of receptors family by vivek sharmaAnimatedWorld
Definition- Receptor are the biologic molecule to which drug bind and produces a measurable response.
So, enzyme and structural proteins can be considerd to be pharmacologic receptors.
Majorly receptor are of 4 types and the molecule or a drug interact to receptor to give response often called as ligand.
The type of receptor a ligand will bind is depend on the nature of ligand.
Hydrophilliic ligand binds to the receptor found on the cell surface.
Hydrophobic ligand can enter the cell membrane to intract the receptor present on inside the cells.
Classification of Receptors
A. Cell surface receptor
Ligand-gated Ion Channel
G Protein Coupled Receptor
Enzyme linked Receptor
B. Intracellular Receptor
Nuclear Receptor
Immunotherapeutics and Humanisation of antibodiesSanju Kaladharan
- Immunotherapeutics aim to activate the body's immune system to fight disease by triggering or mimicking immune responses. They include cytokines, monoclonal antibodies, antibody conjugates, and antibody-directed enzyme prodrug therapy.
- Monoclonal antibodies can directly induce cell death or block growth receptors. They also recruit immune cells through antibody-dependent cytotoxicity and complement-dependent cytotoxicity.
- Early monoclonal antibodies were murine but caused human anti-mouse antibody responses. Newer techniques generate chimeric antibodies by combining mouse and human portions or fully human antibodies from libraries or transgenic mice to reduce this immune response.
The JAK-STAT signaling pathway transmits signals from extracellular chemical signals to the cell nucleus, which leads to DNA transcription and cellular activity. It consists of receptors, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When ligands bind to receptors, JAKs phosphorylate themselves and STATs, causing STAT dimers to enter the nucleus and promote transcription. Disrupted JAK-STAT signaling can cause immune deficiency and cancer. Drugs targeting JAK-STAT are used to reduce immune response and treat disorders like cancer and rheumatoid arthritis.
The MAPK pathway is a signal transduction pathway that responds to extracellular stimuli and regulates various cellular processes. It involves a phosphorylation cascade from MAPKKK to MAPKK to MAPK that ultimately regulates transcription factors and gene expression. Second messengers like cAMP, IP3, and calcium amplify extracellular signals and allow cross-talk between different pathways. The MAPK pathway controls processes like cell growth, division, survival, and metabolism.
AMP-activated protein kinase (AMPK) is an enzyme that acts as a cellular energy sensor. It is activated by increases in the AMP:ATP ratio caused by metabolic stresses that deplete ATP. When activated, AMPK works to switch on catabolic pathways that generate ATP while switching off ATP-consuming processes like biosynthesis. AMPK activation improves blood glucose and lipid levels, making it a promising target for treating diabetes and other metabolic disorders. AMPK regulates glucose and lipid metabolism in the liver, skeletal muscle, pancreas and hypothalamus.
The document summarizes different types of cell death including programmed cell death (PCD), apoptosis, necrosis, and autophagy. It describes key aspects of apoptosis such as the intrinsic and extrinsic pathways, the role of caspases and Bcl-2 proteins, mitochondrial involvement, and morphological changes cells undergo during apoptosis. Necrosis is described as unprogrammed cell death caused by external factors like trauma or infection. Autophagy is noted as another form of programmed cell death.
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are intracellular second messengers that mediate the effects of various hormones and neurotransmitters. cAMP mediates processes like steroidogenesis, secretion, ion transport and gene regulation through protein kinase A (PKA)-catalyzed phosphorylation of substrates. cGMP is involved in processes like vision, smooth muscle relaxation and vasodilation through protein kinase G (PKG). Both cAMP and cGMP signals are terminated by phosphodiesterases, which hydrolyze them. Phosphatases also regulate phosphorylation state of substrates.
This document provides an overview of signal transduction mechanisms. It discusses various types of receptors including G protein-coupled receptors, receptor tyrosine kinases, integrins, toll-like receptors and ligand-gated ion channels. It describes how extracellular ligands bind to cell surface receptors and initiate intracellular signaling pathways such as the cAMP pathway and phosphatidylinositol pathway. Defects in these signaling pathways can lead to diseases. The document provides details on the mechanisms of G protein-coupled receptor signaling and downstream effects.
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
Applications of Genomic and Proteomic ToolsRaju Paudel
This document provides an overview of genomic and proteomic tools. It discusses topics like genomics, which is the study of genomes including structural and functional genomics. Proteomics is defined as the large-scale study of proteins, their structures and functions. Several techniques are described briefly, including DNA gel electrophoresis, polymerase chain reaction (PCR), real-time PCR, DNA sequencing, microarray technology, enzyme-linked immunosorbent assay (ELISA), and blotting techniques like Southern blotting, Northern blotting and Western blotting. Applications of these various tools are also mentioned.
Jump to search
The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors (which bind the chemical signals).[1] Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
This document discusses cell signaling via cyclic AMP (cAMP) pathways. It begins by explaining primary and secondary messengers, with an emphasis on the role of cAMP as a secondary messenger. It then describes the steps of the cAMP pathway in detail, including the G protein-coupled receptor, activation of adenylyl cyclase and conversion of ATP to cAMP, activation of protein kinase A by cAMP, and regulation of glycogen metabolism. The document discusses mechanisms of feedback regulation of the cAMP pathway to terminate the cellular response, such as receptor desensitization and degradation of cAMP by phosphodiesterase.
This document summarizes kinase receptors and nuclear receptors. Kinase receptors contain an extracellular ligand-binding domain connected by a transmembrane helix to an intracellular domain with kinase activity. They signal through phosphorylation cascades like MAPK. Nuclear receptors regulate gene transcription as ligand-activated transcription factors. They contain a ligand binding domain, DNA binding domain, and transcriptional regulation domain. Nuclear receptors form dimers and recruit cofactors to modify gene expression.
Secondary messengers are intracellular signaling molecules that are released within cells in response to extracellular signaling molecules known as first messengers like hormones and neurotransmitters. Common examples include cyclic AMP, inositol trisphosphate, diacylglycerol, and calcium ions. These secondary messengers help amplify and propagate intracellular signals by binding to target proteins and modulating their activity, often through phosphorylation. They allow cells to mount robust physiological responses despite the extracellular signals not directly crossing the cell membrane.
Nuclear receptor type I are intracellular receptors found in the cytoplasm that respond to hydrophobic ligands. When ligands bind, the receptor-ligand complex undergoes a conformational change that exposes a DNA-binding site, allowing it to move to the nucleus and bind to specific regulatory regions of DNA to promote transcription of genes without needing to pass the signal to other proteins. Nuclear receptors can function as monomers, homodimers, or heterodimers to regulate transcription.
G Protein–Coupled Receptors (GPCRs) are integral membrane proteins that are activated by extracellular signaling molecules and activate intracellular secondary messenger pathways. They have seven transmembrane domains and activate heterotrimeric G proteins upon ligand binding. The G protein then activates downstream effector enzymes like adenylyl cyclase, which generates secondary messengers like cAMP. These messengers go on to activate pathways that ultimately alter cell function. The beta-adrenergic receptor pathway is a key example, with epinephrine binding and cAMP production leading to protein kinase A activation. PKA then phosphorylates target proteins to produce effects like increased heart rate. GPCRs are major drug targets, and their deregulation
Introduction to Genetic Variation in GPCR
G-Protein couple Receptor
Genetic variation in GPCRs
V2 Vasopressin Receptor, Thrombroxane Receptor, P2Y 12ADP Receptor, Chemokine Receptor, Biogenic amine receptors
Presented by
R. REKHA
Department of Pharmacology
This document summarizes the JAK-STAT signaling pathway. It describes that the pathway involves Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins that communicate chemical signals from outside the cell to the cell's nucleus. The JAK-STAT pathway is involved in processes like immunity, cell division, cell death, and tumor formation. Disruptions to the pathway can lead to diseases affecting the skin, immune system, and cancers. The document outlines the key steps of the pathway including cytokine binding, JAK phosphorylation, STAT phosphorylation and dimerization, STAT transport to the nucleus to act as a transcription factor.
The JAK-STAT signaling pathway transmits signals from extracellular chemicals to the nucleus, activating transcription of target genes. It consists of a cell surface receptor, associated Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When a ligand binds the receptor, JAKs phosphorylate STATs, which form dimers and translocate to the nucleus to regulate gene expression. The Ras/MAPK pathway similarly relays signals from cell surface receptors via Ras, Raf, MEK, and MAPK proteins to influence transcription. Both pathways are tightly regulated and important for processes like cell growth, differentiation, and apoptosis, with dysregulation contributing to diseases.
Classification of receptors family by vivek sharmaAnimatedWorld
Definition- Receptor are the biologic molecule to which drug bind and produces a measurable response.
So, enzyme and structural proteins can be considerd to be pharmacologic receptors.
Majorly receptor are of 4 types and the molecule or a drug interact to receptor to give response often called as ligand.
The type of receptor a ligand will bind is depend on the nature of ligand.
Hydrophilliic ligand binds to the receptor found on the cell surface.
Hydrophobic ligand can enter the cell membrane to intract the receptor present on inside the cells.
Classification of Receptors
A. Cell surface receptor
Ligand-gated Ion Channel
G Protein Coupled Receptor
Enzyme linked Receptor
B. Intracellular Receptor
Nuclear Receptor
Immunotherapeutics and Humanisation of antibodiesSanju Kaladharan
- Immunotherapeutics aim to activate the body's immune system to fight disease by triggering or mimicking immune responses. They include cytokines, monoclonal antibodies, antibody conjugates, and antibody-directed enzyme prodrug therapy.
- Monoclonal antibodies can directly induce cell death or block growth receptors. They also recruit immune cells through antibody-dependent cytotoxicity and complement-dependent cytotoxicity.
- Early monoclonal antibodies were murine but caused human anti-mouse antibody responses. Newer techniques generate chimeric antibodies by combining mouse and human portions or fully human antibodies from libraries or transgenic mice to reduce this immune response.
The JAK-STAT signaling pathway transmits signals from extracellular chemical signals to the cell nucleus, which leads to DNA transcription and cellular activity. It consists of receptors, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When ligands bind to receptors, JAKs phosphorylate themselves and STATs, causing STAT dimers to enter the nucleus and promote transcription. Disrupted JAK-STAT signaling can cause immune deficiency and cancer. Drugs targeting JAK-STAT are used to reduce immune response and treat disorders like cancer and rheumatoid arthritis.
The MAPK pathway is a signal transduction pathway that responds to extracellular stimuli and regulates various cellular processes. It involves a phosphorylation cascade from MAPKKK to MAPKK to MAPK that ultimately regulates transcription factors and gene expression. Second messengers like cAMP, IP3, and calcium amplify extracellular signals and allow cross-talk between different pathways. The MAPK pathway controls processes like cell growth, division, survival, and metabolism.
AMP-activated protein kinase (AMPK) is an enzyme that acts as a cellular energy sensor. It is activated by increases in the AMP:ATP ratio caused by metabolic stresses that deplete ATP. When activated, AMPK works to switch on catabolic pathways that generate ATP while switching off ATP-consuming processes like biosynthesis. AMPK activation improves blood glucose and lipid levels, making it a promising target for treating diabetes and other metabolic disorders. AMPK regulates glucose and lipid metabolism in the liver, skeletal muscle, pancreas and hypothalamus.
The document summarizes different types of cell death including programmed cell death (PCD), apoptosis, necrosis, and autophagy. It describes key aspects of apoptosis such as the intrinsic and extrinsic pathways, the role of caspases and Bcl-2 proteins, mitochondrial involvement, and morphological changes cells undergo during apoptosis. Necrosis is described as unprogrammed cell death caused by external factors like trauma or infection. Autophagy is noted as another form of programmed cell death.
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are intracellular second messengers that mediate the effects of various hormones and neurotransmitters. cAMP mediates processes like steroidogenesis, secretion, ion transport and gene regulation through protein kinase A (PKA)-catalyzed phosphorylation of substrates. cGMP is involved in processes like vision, smooth muscle relaxation and vasodilation through protein kinase G (PKG). Both cAMP and cGMP signals are terminated by phosphodiesterases, which hydrolyze them. Phosphatases also regulate phosphorylation state of substrates.
This document provides an overview of signal transduction mechanisms. It discusses various types of receptors including G protein-coupled receptors, receptor tyrosine kinases, integrins, toll-like receptors and ligand-gated ion channels. It describes how extracellular ligands bind to cell surface receptors and initiate intracellular signaling pathways such as the cAMP pathway and phosphatidylinositol pathway. Defects in these signaling pathways can lead to diseases. The document provides details on the mechanisms of G protein-coupled receptor signaling and downstream effects.
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
GPCRs activate secondary messenger systems through G proteins. When a ligand binds a GPCR, it activates an associated G protein which then activates downstream effectors like adenylyl cyclase or phospholipase C. These effectors produce second messengers, mainly cAMP or IP3 and diacylglycerol, which activate protein kinases and trigger cellular responses. PKA is activated by cAMP and phosphorylates target proteins, while IP3 mobilizes calcium from intracellular stores. These second messenger systems allow GPCRs to regulate diverse physiological processes.
This Slide gives you a idea about the subject Cellular and Molecular pharmacology where the cell signalling, secondary messengers and its intracellular signalling pathways has been celarly explained
1. The document discusses signal transduction and second messengers. It provides examples of epinephrine, insulin, and epidermal growth factor signaling pathways.
2. Key steps in signal transduction pathways include the release of a primary messenger like a hormone, reception by cell surface receptors, transmission of the signal inside the cell by a second messenger, activation of effector proteins, and termination of the signal.
3. Epinephrine signaling involves G protein coupled receptors that activate adenylate cyclase via G proteins, increasing cyclic AMP and activating protein kinase A. Insulin signaling activates its receptor tyrosine kinase, initiating a phosphorylation cascade. Calcium is also a widespread second messenger that activates proteins like calmodulin
Signal transduction begins with ligand binding to a receptor on the cell surface. This triggers a series of molecular events within the cell through second messengers like cAMP or IP3. These second messengers activate intracellular pathways that ultimately result in changes in cell function or gene expression. The two major pathways are the cAMP pathway which activates protein kinase A, and the phosphatidylinositol pathway which activates protein kinase C through IP3 and calcium release. These second messenger systems allow cells to respond appropriately to signals from other cells.
G protein coupled receptor and pharmacotherapeuticspriyanka527
This document provides an overview of G-protein coupled receptors (GPCRs) and their role in cell signaling. It discusses the history and structure of GPCRs, how they interact with G-proteins and secondary messengers like cAMP and IP3 to activate intracellular signaling pathways. These pathways regulate key cellular processes and are targets for drug development to treat diseases. The document also categorizes different classes of GPCRs and summarizes the mechanisms and physiological roles of various secondary messenger systems like cAMP, IP3, and ion channels in signal transduction.
Second messengers are small intracellular molecules that amplify signals received at cell surface receptors and help transmit them to target molecules inside the cell. The document discusses four main classes of second messengers - cyclic nucleotides, membrane lipid derivatives, calcium ions, and gases like nitric oxide. It provides details on several important second messengers, including cAMP, cGMP, IP3, DAG, and calcium ions, and how they mediate intracellular signaling pathways and cellular responses.
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
Receptors are binding sites located on cells that bind specific molecules and initiate responses. There are several types of receptors including ionotropic receptors that act as ligand-gated ion channels, G protein-coupled receptors that activate intracellular signaling pathways via G proteins, and intracellular or nuclear receptors that directly influence gene expression. Receptor binding involves various interaction forces and leads to responses by altering cellular functions. Understanding receptor pharmacology is crucial for explaining how drugs produce their effects.
The document discusses second messenger systems. It describes how second messengers relay signals from cell surface receptors to target molecules inside the cell. Some key points discussed include:
- Earl Sutherland discovered cyclic AMP (cAMP) as the second messenger for epinephrine and won the Nobel Prize for this work.
- Common second messenger systems include those using cAMP, cGMP, phosphatidylinositol, and tyrosine kinases as secondary messengers.
- G proteins act as transducers between receptors and effectors and are important drug targets.
- cAMP and cGMP have several downstream targets including protein kinases that phosphorylate other proteins and regulate various cellular processes.
The document discusses different types of receptors and how they function. It describes transmembrane receptors like G protein-coupled receptors and ionotropic receptors. It also discusses intracellular receptors like nuclear receptors and receptor tyrosine kinases. The key concepts covered are how ligands bind to receptors and the downstream cell signaling pathways that are activated, including G proteins, second messengers like cAMP and IP3/DAG, and transcriptional regulation. Receptor properties like affinity, efficacy, desensitization, and regulation are also summarized.
The document summarizes key aspects of signal transduction pathways involving smooth muscle relaxation. It describes how acetylcholine binds to receptors on endothelial cells, activating a G protein which signals the production of nitric oxide (NO). NO then diffuses into the smooth muscle cell where it binds receptors and activates guanylate cyclase, increasing cGMP levels. cGMP activates protein kinase G, which phosphorylates calcium channels and causes them to close. With reduced calcium levels, the smooth muscle relaxes. The document also provides an overview of different receptor types, molecular switches in pathways, and differences between heterotrimeric and small G proteins.
Second messengers are small intracellular molecules that amplify signals received at cell surface receptors and help transmit them to target molecules within the cell. They include cyclic nucleotides like cAMP and cGMP, calcium ions, inositol trisphosphate, diacylglycerol, and nitric oxide. These second messengers activate intracellular enzyme and protein targets that trigger cellular responses like changes in metabolism, gene expression, and cell growth. Earl Sutherland discovered cAMP as the first second messenger and won the 1971 Nobel Prize for this foundational discovery in cell signaling pathways.
G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors. Upon ligand binding, GPCRs activate intracellular G proteins that propagate signals via second messenger molecules. There are three major families of G proteins - Gs stimulates adenylate cyclase and increases cAMP, Gi inhibits adenylate cyclase and decreases cAMP, and Gq activates phospholipase C and increases intracellular calcium. Receptor tyrosine kinases (RTKs) activate intracellular signaling pathways through autophosphorylation upon ligand binding, which recruits signaling proteins containing SH2 domains. Major RTK pathways include Ras-MAPK, which regulates cell growth and proliferation.
1. Glycogenesis is the process of glycogen synthesis, the storage form of carbohydrates in animals and plants.
2. Glycogen is synthesized from glucose-1-phosphate through the addition of glucose units via alpha-1,4 glycosidic bonds and branching via alpha-1,6 bonds, forming a branched polymer structure.
3. Glycogenesis occurs primarily in the liver and muscles, with liver glycogen functioning to regulate blood glucose levels between meals through glycogenolysis and export of glucose, while muscle glycogen provides glucose for local glycolysis.
The document discusses various types of signal transduction in cells. It describes how extracellular signals like hormones bind to cell surface receptors and trigger intracellular signaling pathways using second messengers. These pathways involve G proteins and the production of molecules like cyclic AMP and inositol triphosphates to activate enzymes like protein kinase A and C. This leads to changes in gene expression, metabolism and cell behavior in response to extracellular signals.
Receptor molecules have three domains: an extracellular ligand-binding domain, a transmembrane domain, and a cytoplasmic domain. G-protein coupled receptors have seven transmembrane alpha helices and activate intracellular signaling pathways by coupling to heterotrimeric G proteins. When a ligand binds to the receptor, it causes a G protein's alpha subunit to exchange GDP for GTP and dissociate from the beta-gamma subunits to activate downstream effector molecules like adenylyl cyclase or phospholipase C. These effectors generate second messengers such as cAMP or IP3/DAG to amplify the signal and regulate cellular processes.
Glycolysis is the catabolic pathway that converts glucose into pyruvate, generating a small amount of ATP. It occurs in two phases:
1) The energy investment phase uses two ATP molecules to phosphorylate and split glucose into two 3-carbon glyceraldehyde-3-phosphate molecules.
2) The energy generation phase oxidizes the glyceraldehyde molecules to form two pyruvate molecules along with two NADH molecules and four ATP molecules. Overall, glycolysis generates two ATP molecules per glucose molecule. Key regulatory enzymes include hexokinase, phosphofructokinase, and pyruvate kinase.
Similar to secondary messengers and intracellular signaling (20)
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Travis Hills of MN is Making Clean Water Accessible to All Through High Flux ...Travis Hills MN
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Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
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Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.
CLASS 12th CHEMISTRY SOLID STATE ppt (Animated)eitps1506
Description:
Dive into the fascinating realm of solid-state physics with our meticulously crafted online PowerPoint presentation. This immersive educational resource offers a comprehensive exploration of the fundamental concepts, theories, and applications within the realm of solid-state physics.
From crystalline structures to semiconductor devices, this presentation delves into the intricate principles governing the behavior of solids, providing clear explanations and illustrative examples to enhance understanding. Whether you're a student delving into the subject for the first time or a seasoned researcher seeking to deepen your knowledge, our presentation offers valuable insights and in-depth analyses to cater to various levels of expertise.
Key topics covered include:
Crystal Structures: Unravel the mysteries of crystalline arrangements and their significance in determining material properties.
Band Theory: Explore the electronic band structure of solids and understand how it influences their conductive properties.
Semiconductor Physics: Delve into the behavior of semiconductors, including doping, carrier transport, and device applications.
Magnetic Properties: Investigate the magnetic behavior of solids, including ferromagnetism, antiferromagnetism, and ferrimagnetism.
Optical Properties: Examine the interaction of light with solids, including absorption, reflection, and transmission phenomena.
With visually engaging slides, informative content, and interactive elements, our online PowerPoint presentation serves as a valuable resource for students, educators, and enthusiasts alike, facilitating a deeper understanding of the captivating world of solid-state physics. Explore the intricacies of solid-state materials and unlock the secrets behind their remarkable properties with our comprehensive presentation.
Discovery of An Apparent Red, High-Velocity Type Ia Supernova at 𝐳 = 2.9 wi...Sérgio Sacani
We present the JWST discovery of SN 2023adsy, a transient object located in a host galaxy JADES-GS
+
53.13485
−
27.82088
with a host spectroscopic redshift of
2.903
±
0.007
. The transient was identified in deep James Webb Space Telescope (JWST)/NIRCam imaging from the JWST Advanced Deep Extragalactic Survey (JADES) program. Photometric and spectroscopic followup with NIRCam and NIRSpec, respectively, confirm the redshift and yield UV-NIR light-curve, NIR color, and spectroscopic information all consistent with a Type Ia classification. Despite its classification as a likely SN Ia, SN 2023adsy is both fairly red (
�
(
�
−
�
)
∼
0.9
) despite a host galaxy with low-extinction and has a high Ca II velocity (
19
,
000
±
2
,
000
km/s) compared to the general population of SNe Ia. While these characteristics are consistent with some Ca-rich SNe Ia, particularly SN 2016hnk, SN 2023adsy is intrinsically brighter than the low-
�
Ca-rich population. Although such an object is too red for any low-
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cosmological sample, we apply a fiducial standardization approach to SN 2023adsy and find that the SN 2023adsy luminosity distance measurement is in excellent agreement (
≲
1
�
) with
Λ
CDM. Therefore unlike low-
�
Ca-rich SNe Ia, SN 2023adsy is standardizable and gives no indication that SN Ia standardized luminosities change significantly with redshift. A larger sample of distant SNe Ia is required to determine if SN Ia population characteristics at high-
�
truly diverge from their low-
�
counterparts, and to confirm that standardized luminosities nevertheless remain constant with redshift.
Discovery of An Apparent Red, High-Velocity Type Ia Supernova at 𝐳 = 2.9 wi...
secondary messengers and intracellular signaling
1. 9/14/2017
1
PRESENTATION ON
SECONDARY MESSENGERS AND
INTRACELLULAR SIGNALING
SUBMITTED TO
DR. GOVIND SINGH
SUBMITTED BY
NIDHI
M.PHARM 1st yr
DEPARTMENT OF PHARMACEUTICAL
SCIENCES
MAHARSHI DAYANAND UNIVERSITY
3. PRIMARY MESSENGERS SECONDARY MESSENGERS
9/14/2017
Extracellular factor like
hormones, or neurotransmitter
such as epinephrine, growth
hormones and serotonin.
Peptide hormones and
neurotransmitter are hydrophilic.
Physically cannot cross the
phospholipids bilayer
These are intermediate molecules
like cyclic AMP or cyclic GMP
When hormones bind to the target
cell receptor, then the cell release
or creates these intermediates
which then stimulate cell response
Pathway involve- SIGNAL
TRANSDUCTION PATHWAY
3
TYPES OF MESSENGERS
5. HYDROPHOBIC MESSENGERS
9/14/2017
5
Diacylglycerol –stimulate protein kinase c activity by
greatly increasing the affinity of the enzyme for
calcium ion
Known target protein include calmodulin the glucose
transporter, HMG-COA reductase
6. PHOSPHATIDYLINOSITOL
9/14/2017
6
Phosphatidylinositol negative charged phospholipid
and a minor component in eukaryotic cell
membranes
The inositol can be phosphorylated to form:
Phosphatidylinositol-4-phosphate
Phosphatidylinositol-4,5-biphosphate
Phosphatidylinositol-3,4,5-triphosphate
8. G- PROTEIN
9/14/2017
8
Level of middle management in the cellular
organization and are able to communicate between
receptor and the effector enzymes or ion channels
They were called G-PROTEIN because of their
interaction with the guanine nucleotides, GTP and
GDP
The G protein are bound to the cytoplasmic surface
of the plasma membrane
Heterotrimeric molecules consisting 2α, β,γ
9. 9/14/20179
subtype Location of receptor
Type of G
protein coupled
receptor
Basic pathways
α1 Smooth muscle Gq Increase in PLC,
Increase in
intracellular
calcium ion
contraction
α2 Presynaptic nerves Gi Decrease in
activation of AC
Decrease in cyclic
AMP
β1
β2
β3
Heart
Smooth muscle
Fat tissue
Gs
Increase in
activation of AC,
Increase in cyclic
AMP, increase
intracellular
signaling pathways
11. GPCR SIGNALING PATHWAY
9/14/2017
11
Ligand bind to the receptor altering its conformation
and increasing its affinity for the G protein to which
its binds
G subunit release it GDP which is replaced by GTP
Alpha subunit dissociate from the G complex and
bind to an effector activating the effector
12. CONTINUED……
9/14/2017
12
Activated AC produce cyclic AMP
GTPase activity of G protein hydrolyzes the bound
GTP deactivating G
G reassociates with G reforming the trimeric G
protein and the effector ceases its activity
14. ADENYLYL CYCLASE:CAMP PATHWAY
9/14/2017
14
cAMP is a secondary messenger that is synthesized
from ATP by the action of the cAMP- dependent
protein kinase
Which increase contractility, impulse generation,
lipolysis
16. IP3- DAG PATHWAY
9/14/2017
16
IP3 located on endoplasmic reticulum
Responsible for protein and lipid synthesis
DAG- directly activate protein kinase c and control
phosphorylation of amino acid of variety of
intracellular protein
Causes smooth muscle contraction
18. CYCLIC GMP
9/14/2017
18
Cyclic guanosine monophosphate is a cyclic
nucleotide derived from GTP
Common regulator of ion channel, conductance,
glycogenolysis, and cellular apoptosis
It also relaxes smooth muscles tissue
In blood vessels relaxation of vascular smooth
muscles lead to vasodilation and increase blood flow
21. CALCIUM ION
9/14/2017
21
Great important amongest many other intracellular
secondary messengers
Calcium ion bind with calmodulin(intracellular)
Activate
MLCK(myosin light chain kinase)
22. Continued………..
9/14/2017
22
Smooth muscle contraction
Calcium ion involved in release of arachidonic acid
from membrane phospholipid by activated
phospholipase and initiate the synthesis of
prostaglandin and leukotrienes
Calcium ion synergize with PKC
Activation of cellular function like hepatocyte,
glycogenolysis, insulin release from pancreas
Imp. Role in contraction of smooth muscles
24. GASEOUS SIGNALING
9/14/2017
24
Either synthesized internally in the organism, tissue,
or cell or are received by the organism
Induce certain physiological or biochemical changes
in the organism, tissue or cell
Ex carbon monoxide, nitric oxide, hydrogen sulphide
25. NITRIC OXIDE
9/14/2017
25
Known as endothelium derived relaxing factor is
biosynthesized from L-arginine, oxygen & NADPH
by various NO synthase enzymes
The endothelium(inner lining) of blood vessel use
NO to signal the surrounding smooth muscle
Result in vasodilation and increase blood flow
26. CONTINUED…..
9/14/2017
26
NO highly reactive its life time is of few sec yet it
diffuses freely across membrane
For body to generate nitric oxide through nitrate-
nitrite-nitric oxide pathway
Reduction of nitrate to nitrite occur in mouth by
bacteria
Monitoring NO status by saliva testing detect the
bioconversion of plant derived nitrate into nitric
oxide
27. CONTINUED……..
9/14/2017
27
Production of NO is elevated in population living at
high altitudes which help these people to avoid
hypoxia by aiding in pulmonary vasodilation
Nitroglycerin and amyl nitrite serves as vasodilator
because they converted to NO in the body
Vasodilating antihypertensive drug minoxidil
contain an NO moiety act as an NO agonist
28. HYDROGEN SULPHIDE
9/14/2017
28
Produced in small amount by some cell of the
mammalian body and has a number of biological
signaling function
The gas is produced from beta- synthase and cysta
thionine gamma lyase
Act as an relaxant of smooth muscle and as an
vasodilator
29. CONTINUED…..
9/14/2017
29
It also active in the brain where it increase the
response of the NMDA receptor and facilitates long
term potentiation
36. INTRACELLULAR SIGNALING PATHWAY
9/14/2017
36
Cyclic AMP signaling Pathway
Mitogen activated protein kinase signaling
Janus kinase (JAK) /Signaling transducer and
activator of transcripton (STAT) signaling pathway
37. Mitogen activated protein kinase signaling
9/14/2017
37
Mitogen activated protein kinases is an enzyme that
translocates the signals to the nucleus and activates
many transcriptional factor by phosphorylating
many different proteins that regulate expression of
important cell cycle and differentiation specific
protein
39. ACTIVATION
9/14/2017
39
Epidermal growth factor (EGF) bind to the (EGFR)
epidermal growth factor receptor in the cell
membrane g
Starting the cascade of signals
Activates MAPK(mitogen activated protein kinase)
also known (ERK)
40. CONTINUED…..
9/14/2017
40
Signal enter the cell nucleus and causes transcription
of DNA
Then expressed as protein
GRB2 growth receptor bound protein 2 is a adapter
protein which involve in signal transduction/cell
communication
41. CONTINUED…….
9/14/2017
41
encoded by this gene bind receptor such as the
epidermal growth factor receptor and contain one
SH2 domain and two SH3 domain
Its two SH3 domain direct complex formation
with/other protein and bind to tyrosine
phosphorylated sequences
42. PATHWAY
9/14/2017
42
Signal pass from activated Ras to a cascade of
protein kinases this cascade transmit signals
downstream from activated Ras protein to MAP
kinase
Then MAP kinase translocates the signal to the
nucleus and activates trancriptional factor this whole
phenomenon called as MAP kinase pathway
43. ACTIVATION OF RAS PROTEIN
9/14/2017
43
RAS is a monomeric GTP binding switch protein that
alternates between active on state with a bound GTP
and inactive off state with a bound GTP
It is not directly linked to receptor
Its activation is accelerated by a guanosine
nucleotide transfer factor
45. HOW (AMPK) GET ACTIVATED
9/14/2017
45
It is activated by increases in the cellular AMP:ATP
ratio caused by metabolic stresses
Muscle contraction leads to increase in AMP/ATP
level to increase in AMPK activity
47. Requirement for signal transduction
9/14/2017
47
Signal –that is to be passed
Receptor-to which ligand binds
Adapter protein-form link between membrane and
bound receptors and protein is to be activated
Protein cascade- that would lead to the activation of
transcriptional factors
Transcriptional factors
49. RECEPTORS
9/14/2017
49
Receptor tyrosine kinases- this type of receptor
contain intrinsic protein tyrosine kinase activity in
their cytosolic domain
These have one extracellular domain which serves as
ligand and one cytosolic domain to which adapter
molecule bind
50. ACTIVATION OF RTKs
9/14/2017
50
Most RTKs are monomeric but ligand binding
induces dimerization of receptors
Formation of ligand receptor complex
Alteration and activation of receptor
51. CONTINUED…..
9/14/2017
51
This conformational changes facilitates binding of
ATP
In dimeric receptor the kinases in one subunit can
phosphorylate one or more tyrosine residues
Phosphorylates other site in the cytosolic domain
Activated RTKs interact with adaptor protein
53. ADAPTER PROTEIN
9/14/2017
53
Small protein that contain sos, GRB2 domain but
have no intrinsic enzymatic or signaling activites
These protein couple activated RTKs
57. THERAPEUTIC POTENTIAL
9/14/2017
57
Type 2 diabetic patient are often associated with
hypertriglyceridaemia and high cholesterol
The potential risk factor for CV problems
Activated AMPK could reduce this risk
58. JAK-STAT SIGNALING PATHWAY
9/14/2017
58
Janus kinase signal transducers and activators of
transcription pathway used to transduce a multitude
of signal for development and homeostasis
JAK activation stimulates cell proliferation,
differentiation, cell migration and apoptosis involve
in various processes such as hematopoiesis immune
development
60. STAT ( signal transduction and activator of
transcriptional factor)
9/14/2017
60
STAT are latent transcriptional factor that reside in the
cytoplasm until activated
STAT conserve tyrosine residue near the c- terminus that
is phosphorylated by JAK
Phosphorylated STAT enter the nucleus by mechanism
that is dependent on nucleoprotein interactor
64. JAK ACTIVATION
9/14/2017
64
JAK activation occur upon ligand mediated receptor
multimerization because two JAK are brought into
close allowing phosphorylation
66. MECHANISM
9/14/2017
66
JAK have tyrosine kinase activity bind to some cell
surfaces cytokine receptor, the binding of the ligand to
the receptor triggers activation of JAK
With increased kinase activity they phosphorylate
tyrosine residues on the receptor STATs
Possessing SH2 domain are recruited to the receptor and
are themselves tyrosine phosphorylated by JAKs
67. CONTINUED…..
9/14/2017
67
Activated STAT dimers accumulate in the cell
nucleus and transcription of their target genes
STAT may also be tyrosine phosphorylated directly
by receptor tyrosine kinases such as the epidermal
growth factor receptor as well as by non receptor
tyrosine kinases such as c-src
The receptor is activated by signal from interferon,
interleukin growth factor or other chemical
messengers
68. REFERENCES
9/14/2017
68
Kobila .K. B ,G protein coupled receptor structure
and activation HHS public access
Murad.F Nitric oxide: the coming of secondary
messenger rambam maimonides medical journal
Rawling.S.J,Rosler.M.K Harrison A.D.The JAK-
STAT signaling pathway journal of cell science
2004117:128,-1283 1292/jcs.00963
Tripathi.K.D Textbook of medical pharmacology
sixth edition jaypee brothers medical publisher page
no 22-37