The R T K R A S M E K Signaling Pathway By Lenard Tardio
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The RTK RAS MEK signaling pathway begins when a ligand binds to a receptor tyrosine kinase (RTK), causing it to dimerize and autophosphorylate. This creates binding sites for the adaptor protein Grb2 and associated protein SOS. The Grb2-SOS complex activates RAS via catalyzing GDP-GTP exchange. Activated RAS recruits RAF to the membrane where it is activated. RAF then phosphorylates MEK, which phosphorylates ERK. ERK phosphorylates transcription factors like ELK-1, leading to expression of genes involved in growth responses. Activated ELK-1 also stimulates a phosphatase to deactivate ERK.
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The document discusses receptor tyrosine kinases (RTKs), a class of cell surface receptors that possess intrinsic tyrosine kinase activity. RTKs are activated through ligand binding and dimerization, which leads to autophosphorylation and downstream signaling. This signaling involves phosphorylation of proteins by RTKs and recruitment of adapter proteins, and results in cellular responses like cell division, differentiation, and motility. Common to all RTKs are an extracellular ligand-binding domain, a transmembrane domain, an intracellular tyrosine kinase domain, and regulatory domains.
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The document discusses receptor tyrosine kinases (RTKs), a class of cell surface receptors that possess intrinsic tyrosine kinase activity. RTKs are activated through ligand binding and dimerization, which leads to autophosphorylation and downstream signaling. This signaling involves phosphorylation of proteins by RTKs and recruitment of adapter proteins, and results in cellular responses like cell division, differentiation, and motility. Common to all RTKs are an extracellular ligand-binding domain, a transmembrane domain, an intracellular tyrosine kinase domain, and regulatory domains.
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The document summarizes the MAPK (mitogen-activated protein kinase) signaling cascade downstream of insulin receptor activation. It discusses:
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2) Ras activates the Raf kinase, which phosphorylates and activates the MEK kinase.
3) MEK then phosphorylates and activates ERK, a MAP kinase that translocates to the nucleus.
4) Nuclear ERK phosphorylates transcription factors like Elk1, stimulating gene transcription required for cell division.
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This document discusses receptor tyrosine kinases (RTKs) and their role in signal transduction. It notes that RTKs are membrane proteins that transmit signals from outside the cell into the cell. When a ligand binds to an RTK, it causes the receptor to dimerize and phosphorylate itself. This activated RTK then transmits the signal by activating downstream proteins like Ras via GRB2 and Sos. Ras further transduces the signal to serine/threonine kinases and transcription factors, ultimately leading to responses in the cell like growth, differentiation, and metabolism. There are 58 known RTK subfamilies involved in various cellular processes.
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Cross talk between signalling pathway
Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another.
This can be achieved through a number of ways with the most common form being crosstalk between proteins of signaling cascades.
In these signal transduction pathways, there are often shared components that can interact with either pathway.
A more complex instance of crosstalk can be observed with transmembrane crosstalk between the extracellular matrix (ECM) and the cytoskeleton.
Receptors with intrinsic protein kinase activity
Receptor tyrosine kinases (RTKs) are cell surface receptors that bind polypeptide growth factors, cytokines, and hormones. They regulate normal cellular processes but also play a critical role in cancer development and progression. There are approximately 20 classes of RTKs that exist as single or multimeric complexes and activate intracellular signaling pathways through autophosphorylation following ligand binding. Mutations in RTKs and their downstream effectors can lead to uncontrolled cell growth by constitutively activating growth signaling pathways. Several RTK inhibitors have been developed for cancer treatment, including those that target specific kinases as well as multi-kinase inhibitors.
signal transduction
1. The document outlines different types of cellular receptors including cell surface receptors like G protein-coupled receptors and tyrosine kinase receptors, as well as intracellular receptors.
2. It provides examples of hormone signaling pathways, noting that hormones activate receptors which then trigger intracellular second messenger systems like cAMP, calcium, or phosphorylation to produce cellular effects.
3. The mechanism of insulin signaling is described as an example of receptor tyrosine kinase activation, showing how insulin binding leads to phosphorylation of intracellular targets and downstream effects on processes like glucose uptake and fat/protein synthesis.
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Signal transduction
GENERAL IDEA OF SIGNAL TRANSDUCTION
DEFINATION
WHAT DOES THE TERM SIGNAL TRANSDUCTION MEANS
HISTORY
BASIC ELEMENTS IN SIGNAL TRANSDUCTION
TYPES OF SIGNAL TRANSDUCTION
SIGNALLING MOLECULE
RECEPTOR MOLECULE
MODES OF CELL CELL SIGNALING
SECOND MESSENGER
SIGNAL TRANSDUCTION PATHWAY
SOME SIGNALING PATHWAYS
SIGNIFICANCE
CONCLUSION
REFERENCE
3.22.2010
The document provides an overview of calcium regulation and receptor tyrosine kinase (RTK) signaling pathways. It describes:
1) Calcium is maintained at low levels (~10^-7M) in the cytoplasm and stored at higher levels (~10^-3M) in the endoplasmic reticulum. Calcium is released through IP3 and ryanodine receptors on organelles and voltage or ligand gated channels on the plasma membrane. Calcium is transported back into storage by ATPase pumps.
2) RTKs dimerize and autophosphorylate when bound by extracellular ligands such as growth factors. This recruits adapter proteins like Grb2 and SOS, activating the Ras/MAPK pathway through
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1. G-proteins bind GTP and control intracellular signaling pathways. They exist in two states - active when bound to GTP and inactive when bound to GDP.
2. G-proteins are tightly regulated by accessory proteins that modulate their cycling between GTP-bound and GDP-bound states.
3. The heterotrimeric G-proteins transmit signals from cell surface receptors to enzymes and channels. They are stimulated by receptors, act on effectors, and are regulated by nucleotide exchange and hydrolysis.
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This document discusses receptors and their downstream signaling pathways, including JAK-STAT and MAPK pathways. It defines receptors and describes different receptor types like G protein-coupled and enzyme-linked receptors. It then focuses on the JAK-STAT pathway, identifying its components like JAK kinases and STAT transcription factors, and drugs that target this pathway for conditions like rheumatoid arthritis. Finally, it examines the MAPK pathway, identifying the MAP kinase families involved in key cellular processes and examples of drugs that inhibit parts of this pathway.
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The document summarizes the MAPK (mitogen-activated protein kinase) signaling cascade downstream of insulin receptor activation. It discusses:
1) Upon insulin binding, the insulin receptor phosphorylates IRS-1, which recruits Grb2 and Sos to activate Ras.
2) Ras activates the Raf kinase, which phosphorylates and activates the MEK kinase.
3) MEK then phosphorylates and activates ERK, a MAP kinase that translocates to the nucleus.
4) Nuclear ERK phosphorylates transcription factors like Elk1, stimulating gene transcription required for cell division.
Tyrosine kinase linked receptors
This document discusses receptor tyrosine kinases (RTKs) and their role in signal transduction. It notes that RTKs are membrane proteins that transmit signals from outside the cell into the cell. When a ligand binds to an RTK, it causes the receptor to dimerize and phosphorylate itself. This activated RTK then transmits the signal by activating downstream proteins like Ras via GRB2 and Sos. Ras further transduces the signal to serine/threonine kinases and transcription factors, ultimately leading to responses in the cell like growth, differentiation, and metabolism. There are 58 known RTK subfamilies involved in various cellular processes.
G protein coupled receptors new
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Deeksha
This document provides an overview of receptor tyrosine kinases (RTKs) and their signaling pathways. It begins with an introduction to cell signaling and the different types of receptors, focusing on protein tyrosine kinases. RTKs are described as high-affinity cell surface receptors that activate upon ligand binding and recruit signal transduction proteins. The mechanisms of RTK activation and recruitment of proteins like Ras are explained. It further details how RTK activation of Ras leads to the Ras/MAP kinase signaling cascade, which regulates processes like cell division and differentiation. The relationships between different signaling pathways that can activate the Ras/MAP kinase cascade are also noted.
Cross talk between signalling pathway
Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another.
This can be achieved through a number of ways with the most common form being crosstalk between proteins of signaling cascades.
In these signal transduction pathways, there are often shared components that can interact with either pathway.
A more complex instance of crosstalk can be observed with transmembrane crosstalk between the extracellular matrix (ECM) and the cytoskeleton.
Receptors with intrinsic protein kinase activity
Receptor tyrosine kinases (RTKs) are cell surface receptors that bind polypeptide growth factors, cytokines, and hormones. They regulate normal cellular processes but also play a critical role in cancer development and progression. There are approximately 20 classes of RTKs that exist as single or multimeric complexes and activate intracellular signaling pathways through autophosphorylation following ligand binding. Mutations in RTKs and their downstream effectors can lead to uncontrolled cell growth by constitutively activating growth signaling pathways. Several RTK inhibitors have been developed for cancer treatment, including those that target specific kinases as well as multi-kinase inhibitors.
signal transduction
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2. It provides examples of hormone signaling pathways, noting that hormones activate receptors which then trigger intracellular second messenger systems like cAMP, calcium, or phosphorylation to produce cellular effects.
3. The mechanism of insulin signaling is described as an example of receptor tyrosine kinase activation, showing how insulin binding leads to phosphorylation of intracellular targets and downstream effects on processes like glucose uptake and fat/protein synthesis.
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The MAP kinase pathway is a three-kinase signalling module that transmits signals from growth factor receptors to the nucleus. When Ras is activated by growth factors, it recruits and activates Raf, the first kinase in the cascade. Raf then activates MEK, which activates ERK. Active ERK translocates to the nucleus and phosphorylates transcription factors, influencing processes like cell proliferation. The three-kinase design allows for signal amplification and transmission from the membrane to the nucleus, while regulatory mechanisms maintain specificity.
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Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor, transmitting a signal into the cell and eliciting a physiological response. There are two major steps: 1) A signaling molecule activates a specific membrane receptor. 2) A second messenger transmits the signal into the cell. Signal transduction depends on membrane proteins and phospholipids. The main types of proteins involved are receptors, G proteins, adenylate cyclase, and protein kinases. Ligand-receptor binding activates a G protein, which activates enzymes like adenylate cyclase to produce secondary messengers like cAMP that go on to activate intracellular proteins and modify cellular activity.
Receptor- ligand gated,enzyme linked, nuclear.
The document discusses three main types of receptors: ligand-gated receptors, enzyme-linked receptors, and nuclear receptors. Ligand-gated receptors include nicotinic acetylcholine receptors and GABAA receptors, which act as ion channels and mediate fast synaptic transmission. Enzyme-linked receptors include tyrosine kinase receptors, JAK/STAT receptors, Toll-like receptors, and guanylyl cyclase receptors, which activate intracellular enzyme pathways to regulate processes like cell growth and inflammation. Nuclear receptors directly bind to DNA and act as transcription factors to regulate gene expression, responding to ligands like steroids, vitamins, and fatty acids.
Signal transduction
GENERAL IDEA OF SIGNAL TRANSDUCTION
DEFINATION
WHAT DOES THE TERM SIGNAL TRANSDUCTION MEANS
HISTORY
BASIC ELEMENTS IN SIGNAL TRANSDUCTION
TYPES OF SIGNAL TRANSDUCTION
SIGNALLING MOLECULE
RECEPTOR MOLECULE
MODES OF CELL CELL SIGNALING
SECOND MESSENGER
SIGNAL TRANSDUCTION PATHWAY
SOME SIGNALING PATHWAYS
SIGNIFICANCE
CONCLUSION
REFERENCE
3.22.2010
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1) Calcium is maintained at low levels (~10^-7M) in the cytoplasm and stored at higher levels (~10^-3M) in the endoplasmic reticulum. Calcium is released through IP3 and ryanodine receptors on organelles and voltage or ligand gated channels on the plasma membrane. Calcium is transported back into storage by ATPase pumps.
2) RTKs dimerize and autophosphorylate when bound by extracellular ligands such as growth factors. This recruits adapter proteins like Grb2 and SOS, activating the Ras/MAPK pathway through
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1. G-proteins bind GTP and control intracellular signaling pathways. They exist in two states - active when bound to GTP and inactive when bound to GDP.
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The details about Translational control. Both prokaryotes and eukaryotes.
It can be helpful for the students of Biotechnology, Genetics, Molecular Biology, Microbiology and othe Biology related courses.
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Mapk pathways
MAP KINASES PATHWAY..Regulation and signalling with a note on mammalian derived protein kinases with a note on JNK/p38/PI3 kinase pathways
Cell signaling
Cell signaling is a complex system of communication that coordinates basic cellular activities and cell actions. It involves signaling molecules that produce responses in target cells through receptor binding. There are three main types of signaling: endocrine, paracrine, and autocrine. Upon receptor activation, various intracellular signal transduction pathways are initiated using second messengers like cAMP, IP3, Ca2+, which activate downstream effector mechanisms to elicit cellular responses. The key pathways include G protein-coupled receptor pathways, tyrosine kinase receptor pathways like Ras/Raf pathway and Jak/Stat pathway. Understanding cell signaling is crucial for treating diseases and engineering tissues.
Beta Globin Gene Cluster
This document discusses the beta globin gene cluster and regulation of hemoglobin expression. It contains the following key points:
1. The beta globin gene cluster is located on chromosome 11p15.5 near the telomeric end and spans 70kb. It contains beta globin genes and regulatory elements that control their expression.
2. Expression of beta globin genes is regulated by transcription factors such as GATA-1, EKLF, and NF-E2 that bind to promoter and enhancer elements. The Locus Control Region (LCR) located upstream of the genes is also important for regulating expression.
3. During development, there is a switch in expression from gamma globin genes
Receptors
Receptors are macromolecules that recognize signal molecules and initiate a response. There are four main receptor families: G-protein coupled receptors, ligand-gated ion channels, enzymatic receptors, and receptors that regulate gene expression. G-protein coupled receptors are the largest family and activate downstream effectors like adenylyl cyclase through G proteins. Ion channel receptors open ion channels upon agonist binding. Enzymatic receptors activate intracellular kinases upon ligand binding. Receptors regulating gene expression translocate to the nucleus and regulate transcription of target genes.
Transcription dna2011
The document summarizes RNA synthesis and post-transcriptional modifications. It discusses how RNA is synthesized from a DNA template in the 5' to 3' direction by RNA polymerases. It also describes the differences between prokaryotic and eukaryotic transcription, such as eukaryotes having multiple RNA polymerases and transcription occurring separately from translation. Specific transcription factors that regulate gene expression by binding to regulatory DNA sequences are also mentioned.
Similar to The R T K R A S M E K Signaling Pathway By Lenard Tardio (20)
6 RTK signaling MAPK Akt.pdfCell signaling presentation
6 RTK signaling MAPK Akt.pdfCell signaling presentation
Cell signalling through MAP-Kinase and JAK STAT pathway.pptx
Cell signalling through MAP-Kinase and JAK STAT pathway.pptx
The R T K R A S M E K Signaling Pathway By Lenard Tardio
- 1. The RTK RAS MEK Signaling Pathway Cytoplasm Extracellular RTK receptors are present in the membrane as monomers Dimerization of the receptor occurs after binding of a bivalent ligand Kinase activity is initiated when the two domains are in close contact allowing for trans-autophosphorilation P P Autophosphorilation sites act as binding sites for signaling proteins The SH2 domain of the adaptor protein Grb2, binds to the phosphorilated tyrosine residues on the RTK Grb2 The SOS protein then binds to the SH3 domain of Grb2. SOS Grb2-SOS The Grb2-SOS complex activates RAS by catalyzing the GTP-GDP exchange Activated RAS starts a MAP Kinase cascade by recruiting the protein RAF to the membrane where it is activated. RAS GDP GTP RAF The MAPKKK RAF, phosphorilates the MAPKK MEK MEK MEK MEK phosphorilates the MAPK ERK ERK ERK ERK phosphorilates transcription factors such as ELK-1 ELK-1 ELK-1 Phosphorilated ELK-1 transcribes genes such as Fos and Jun which are involved in the growth response. Activated ELK-1 stimulates the expression of a gene that encodes a MAPK phosphatase (MKP-1) which deactivates the MAPK ERK. MKP-1 ERK Abbreviation Key: RTK: Receptor protein-tyrosine kinase SH2: Src-homology 2 SH3: Src-homology 3 Grb2: Growth factor receptor-bound protein 2 SOS: Son of sevenless GTP: Guanosine triphosphate GDP: Guanosine diphosphate RAS: Rat sarcoma RAF: proto-oncogene c-RAF ERK: Extracellular-signal-regulated kinases ELK-1: E twenty-six (ETS)-like transcription factor 1 MKP-1: Mitogen-activated protein kinase phosphatase MEK: Dual specificity mitogen-activated protein kinase kinase MAPK: Mitogen-activated protein kinase MAPKK: Mitogen-activated protein kinase kinase MAPKKK: Mitogen-activated protein kinase kinase kinase P: Phosphate Sources: Lecture 5 slides Gerald Karp’s Cell and molecular biology, fifth edition Youtube: www.youtube.com/watch?v=r7GoZ9vFCY8