cell signaling is part of any communication process that governs basic activities of cells and coordinates multiple-cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis
In biology, cell signaling is part of any communication process that governs basic activities of cells and coordinates multiple-cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis.
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.
Cells of multicellular organisms detect and respond to countless internal and extracellular signals that control their growth, division, and differentiation during development, as well as their behavior in adult tissues.
At the heart of all these communication systems are regulatory proteins that produce chemical signals, which are sent from one place to another in the body or within a cell, usually being processed along the way and integrated with other signals to provide clear and effective communication.
Study of cell signaling has traditionally focused on the mechanisms by which eukaryotic cells communicate with each other using extracellular signal molecules such as hormones and growth factors.
Many bacteria, respond to chemical signals that are secreted by their neighbors and accumulate at higher population density. This process, called quorum sensing, allows bacteria to coordinate their behavior, including their motility, antibiotic production, spore formation, and sexual conjugation.
Communication between cells in multicellular organisms is mediated mainly by extracellular signal molecules.
Most cells in multicellular organisms both emit and receive signals. Reception of the signals depends on receptor proteins, usually (but not always) at the cell surface, which bind the signal molecule. The binding activates the receptor, which in turn activates one or more intracellular signaling pathways or systems.
These systems depend on intracellular signaling proteins, which process the signal inside the receiving cell and distribute it to the appropriate intracellular targets.
The targets that lie at the end of signaling pathways are generally called effector proteins, which are altered in some way by the incoming signal and implement the appropriate change in cell behavior.
Depending on the signal and the type and state of the receiving cell, these effectors can be transcription regulators, ion channels, components of a metabolic pathway, or parts of the cytoskeleton.
In biology, cell signaling is part of any communication process that governs basic activities of cells and coordinates multiple-cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis.
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.
Cells of multicellular organisms detect and respond to countless internal and extracellular signals that control their growth, division, and differentiation during development, as well as their behavior in adult tissues.
At the heart of all these communication systems are regulatory proteins that produce chemical signals, which are sent from one place to another in the body or within a cell, usually being processed along the way and integrated with other signals to provide clear and effective communication.
Study of cell signaling has traditionally focused on the mechanisms by which eukaryotic cells communicate with each other using extracellular signal molecules such as hormones and growth factors.
Many bacteria, respond to chemical signals that are secreted by their neighbors and accumulate at higher population density. This process, called quorum sensing, allows bacteria to coordinate their behavior, including their motility, antibiotic production, spore formation, and sexual conjugation.
Communication between cells in multicellular organisms is mediated mainly by extracellular signal molecules.
Most cells in multicellular organisms both emit and receive signals. Reception of the signals depends on receptor proteins, usually (but not always) at the cell surface, which bind the signal molecule. The binding activates the receptor, which in turn activates one or more intracellular signaling pathways or systems.
These systems depend on intracellular signaling proteins, which process the signal inside the receiving cell and distribute it to the appropriate intracellular targets.
The targets that lie at the end of signaling pathways are generally called effector proteins, which are altered in some way by the incoming signal and implement the appropriate change in cell behavior.
Depending on the signal and the type and state of the receiving cell, these effectors can be transcription regulators, ion channels, components of a metabolic pathway, or parts of the cytoskeleton.
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
This Presentation provides an outline knowledge about Cellular Communication, Steps involved, Its Types, Signal Transduction, Secondary Messenger , Receptors with some Interesting Facts and Current Trends. An assignment for the subject, Cellular and Molecular Pharmacology, 1st year M.Pharm, 1st semester.
Cell Signalling Pathway (intra and extra cellular signalling)Aneela Rafiq
the way of communication cell to cell or cell to their environment. they produce some stimuli to correspond to surroundings for survival. Cell signalling helps to defend, survive, production of chemicals and lots of other things. signalling can external and internal. in this presentation, paths are elaborated externally and internally.
Hope it will help to understand cell signal in better way.
Assignment on Need of cell signaling, Steps in cell signaling, Intercellular signaling pathways, Types of intercellular signaling pathways, Intracellular signaling pathways, Receptors, Intercellular and intracellular signaling pathways. Classification of receptor family and molecular structure ligand gated ion channels; Gprotein coupled receptors, tyrosine kinase receptors and nuclear receptors.
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.
Introduction
Definition
History
Basic element in signal transduction
Basic Pathway of signal transduction
Types of signal transduction
Second messenger
Pathway of signal transduction
Conclusion
References
This Presentation provides an outline knowledge about Cellular Communication, Steps involved, Its Types, Signal Transduction, Secondary Messenger , Receptors with some Interesting Facts and Current Trends. An assignment for the subject, Cellular and Molecular Pharmacology, 1st year M.Pharm, 1st semester.
Cell Signalling Pathway (intra and extra cellular signalling)Aneela Rafiq
the way of communication cell to cell or cell to their environment. they produce some stimuli to correspond to surroundings for survival. Cell signalling helps to defend, survive, production of chemicals and lots of other things. signalling can external and internal. in this presentation, paths are elaborated externally and internally.
Hope it will help to understand cell signal in better way.
Assignment on Need of cell signaling, Steps in cell signaling, Intercellular signaling pathways, Types of intercellular signaling pathways, Intracellular signaling pathways, Receptors, Intercellular and intracellular signaling pathways. Classification of receptor family and molecular structure ligand gated ion channels; Gprotein coupled receptors, tyrosine kinase receptors and nuclear receptors.
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.
genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic
Preclinical screening of new substance for pharmacological activityShrutiGautam18
Preclinical study: A study to test a drug, a procedure, or another medical treatment in animals. The aim of a preclinical study is to collect data in support of the safety of the new treatment.
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
Angina pectoris is the medical term for chest pain or discomfort due to coronary heart disease. It occurs when the heart muscle doesn't get as much blood as it needs. This usually happens because one or more of the heart's arteries is narrowed or blocked, also called ischemia.
Angina usually causes uncomfortable pressure, fullness, squeezing or pain in the center of the chest. You may also feel the discomfort in your neck, jaw, shoulder, back or arm. (Many types of chest discomfort — like heartburn, lung infection or inflammation
role of free radicals in human diseases. Inside the human cells, there is an effective antioxidant defence system to counter damaging actions of reactive oxygen species. ... Direct damage to structural proteins and DNA inside the cells may result in loss of cell architecture and lack of its ability to restore.
Anticoagulants, commonly referred to as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time.
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
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3. INTRODUCTION
Cell signaling is part of any communication process that
governs basic activities of cells and coordinates multiple-
cell actions.
The ability of cells to perceive and correctly respond to
their microenvironment is the basis of development,
tissue repair, and immunity, as well as normal tissue
homeostasis.
Errors in signaling interactions and cellular information
processing may cause diseases such as cancer,
autoimmunity, and diabetes
4. CLASSIFICATION
Cell signaling can be classified as either mechanical or
biochemical based on the type of the signal.
Mechanical signals are the forces exerted on the cell and
the forces produced by the cell. These forces can both be
sensed and responded to by the cells.
Biochemical signals are the biochemical molecules such
as proteins, lipids, ions and gases.
5. INTERCELLULAR SIGNALING
Intercellular signal transduction influences nearly every
physiological reaction. It ensures that all cells of a
particular type receive and transform a signal.
In this manner, cells of the same type react
synchronously to a signal. A further function of
intercellular communication is the coordination of
metabolite fluxes between cells of various tissues.
In higher organisms intercellular signaling pathways
have the important task of coordinating and regulating
cell division. The pathways ensure that cells divide
synchronously and, if necessary, arrest cell division and
enter a resting state.
6. INTRACELLULAR SIGNALING
External signals such as hormones or sensory signals are
specifically recognized by receptors that transduce the
external signal into an intracellular signaling chain.
The intracellular signaling paths control all functions of
the cell such as intermediary metabolism, cell division
activity, morphology and the transcription programe.
7.
8. RECEPTOR
Receptor are the sensing element in the system of
chemical communication that coordinates the function of
all the different cell in the body the chemical messenger
being the various hormone, transmitter & other mediator
Many therapeutically useful drug act either as antagonist
or agonist on receptor for know endogenous mediator
9. TYPE OF RECEPTOR
Receptor elicit many different type of cellular effect
Some of them are very rapid such as those involved in
synaptic transmission ,operating within millisecond
where as other receptor mediated effect such as those
produced by thyroid hormone or various steroid
hormones occur over hour or day
Based on molecular structure and the nature of this
linkage
a) Ligand gate ion channel
b) G protein coupled receptor
c) Kinase linked receptor
d) Nuclear receptor
10. LIGAND GATE ION CHANNEL
It is also know as inotropic receptor
a group of trans membrane ion-channel proteins which
open to allow ions such as 𝑁𝑎+
, 𝐾+
, 𝐶𝑎2+
, and 𝐶𝑙−
to
pass through the membrane in response to the binding of
a chemical messenger (i.e. a ligand), such as a
neurotransmitter.
These are the receptor on which fast neurotransmitter act
Ligand binding and channel opening occur on a
millisecond timescale
Example include the nicotine acetylcholine receptor ,
GABA receptor , 5 hydroxytryptamine type 3 receptor
11. MOLECULAR STRUCTURE
The nicotine acetylcholine receptor the first to be cloned
It consist of pentameric assembly of different subunit of
which these are four type termed α, β,γ, δ
Molecular weight 40-50 Kda
The pentameric structure possess two acetylcholine
binding site each lying at interface between one of the
subunit and its neighbor
Both must bind acetylcholine molecule in order for the
receptor to be activate
Each subunit span the membrane four time so the
channel comprise no fewer then 20 membrane spanning
a central pores
12.
13. G PROTEIN COUPLED RECEPTOR
G protein-coupled receptors (GPCRs), also known as seven-
(pass)-transmembrane domain receptors, 7TM receptors,
heptahelical receptors, serpentine receptor, and G protein–
linked receptors (GPLR), constitute a large protein family of
receptors that detect molecules outside the cell and activate
internal signal transduction pathways and, ultimately, cellular
responses. Coupling with G proteins, they are called seven-
transmembrane receptors because they pass through the cell
membrane seven times.
G protein-coupled receptors are found only in eukaryotes,
including yeast, choanoflagellates ,and animals.
G protein-coupled receptors are involved in many diseases.
14.
15. MOLECULAR STRUCTURE
G protein coupled receptor consist of a single
polypeptide chain of up to 1100
Their characteristic structure comprise seven trans
membrane α helices
G protein coupled receptor are divided into three distinct
families
They share the same seven helix structure but differ in
other principally in the length of the extracellular N
terminal and the location of the agonist binding domain
16. Family Receptor Structural
feature
A: rhodospin family The largest group
receptor for most amine
neurotransmitter many
neuropeptide purine
,prostanoid ,cannabinoids
Short extracellular tail
ligand bind to trans
membrane helices or to
extracellular loops
B: secretin/glucagon
receptor family
Receptor for peptide
hormones including
secretin ,glucagon,
calcitonin
Intermediate extra cellar
tail incorporating ligand
binding domain
C: metabotropic
glutamate receptor
/calcium sensor family
Small group metabotropic
glutamate receptor ,
GAB 𝐴 𝐵 receptor, 𝐶𝑎2+
sensing receptor
Long extracellular tail
incorporating ligand
binding domain
17. G PROTEIN AND THEIR ROLE
G Protein comprise a family of membrane resident
protein whose function is to recognize activated GPCRs
and pass on the message to the effector system that
generate a cellular response
They represent the level of middle management in the
organizational hierarchy intervening between the
receptor –choosy mandarin alert to the faintest whiff of
their preferred chemical – and effector enzymes or ion
channel – the blue collar brigade that get the job done
without needing to know which hormones authorized the
process
18. KINASE LINKED AND RELATED RECEPTOR
These membrane receptor are quite different in structure
and function from either the ligand gate channel or the
GPCRs
They mediate the action of wide variety of protein
mediator including growth factor and cytokines and
hormones such as insulin whose effect are exerted
mainly at the level of gene transcription
Most of these receptor are large chain protein consisting
of single chain of up to 1000 residue with single
membrane spanning helical region associated with a
large extracellular ligand binding domain and an
intracellular domain of variable size and function
19. The main type are as follow
1) Receptor tyrosine kinase
2) Serine/ threonine kinase
3) Cytokinse receptor
1. Receptor tyrosine kinase
These receptor have the basic structure incorporating a
tyrosin kinase moiety in the intracellular region they
include receptor for many growth factor such as
epidermal growth factor and nerve factor and also the
group of toll- like receptor that recognize bacterial
lipopolysaccaride and play important role in the body
reaction to infection . The insulin receptor also belong to
the RTK class although it has a more complex domain
20. 2. Serine/ threonine kinase
This smaller class is similar in structure to RTK but
phosphorylate serine and threonine residue rather than
tyrosine. The main example is the receptor for
transforming growth factor (TGF)
3. Cytokinase receptor
These receptor lack enzyme activity . When occupied
they associate with activate a cytosolic tyrosine kinase
such as Jak or other kinase . Ligand for these receptor
include cytokinase such as interferon's and colony-
stimulating factor involved in immunological reponses
21.
22. NUCLEAR RECEPTOR
The fourth type of receptor belong to the nuclear
receptor family
By the 1970 it was clear that receptor for steroid
hormone such estrogen and the glucocorticoid were
present in the cytoplasm of cell and translocate into the
nucleus after binding with their steroid partner
Other hormones such as the thyroid hormone and fat
soluble vitamin D and A were found to act in a similar
fashion
NRs such as the glucocorticoid and retinoic acid receptor
whose ligand were well characterized this family include
a great many orphan receptor
23.
24. SECONDARY MESSENGER
Secondary messenger are intercellular signaling molecule released
by the cell to trigger physiological change such as proliferation ,
Differentiation ,migration , survival and apopties
Secondary messenger are therefore one of the initiating component
of intracellular signal transduction cascade
Example of secondary messenger include cyclic AMP, cyclic GMP,
calcium ion , inositol 1,4,5- trisphosphate and diacylglycerol
25. CYCLIC AMP
Cyclic adenosine 3′,5′-monophosphate (cAMP) was the
first second messenger to be identified and plays
fundamental roles in cellular responses to many
hormones and neurotransmitters .
The intracellular levels of cAMP are regulated by the
balance between the activities of two enzymes : adenylyl
cyclase (AC) and cyclic nucleotide phosphodiesterase
(PDE).
Different isoforms of these enzymes are encoded by a
large number of genes, which differ in their expression
patterns and mechanisms of regulation, generating cell-
type and stimulus-specific responses
26. CYCLIC GMP
Cyclic guanosine monophosphate (cGMP) is a cyclic
nucleotide derived from guanosine triphosphate (GTP).
cGMP acts as a second messenger much like cyclic
AMP. Its most likely mechanism of action is activation
of intracellular protein kinases in response to the binding
of membrane-impermeable peptide hormones to the
external cell surface
27. INOSITOL 1,4,5-TRISPHOSPHATE
inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P
or IP3 is an inositol phosphate signaling molecule.
It is made by hydrolysis of phosphatidylinositol 4,5-
bisphosphate (PIP2), a phospholipid that is located in the
plasma membrane, by phospholipase C (PLC).
Together with diacylglycerol (DAG), IP3 is a second
messenger molecule used in signal transduction in
biological cells.
While DAG stays inside the membrane, IP3 is soluble
and diffuses through the cell, where it binds to its
receptor, which is a calcium channel located in the
endoplasmic reticulum. .
28. SIGNALING PATHWAY
Increases in the intracellular 𝐶𝑎2+ concentrations are
often a result of IP3 activation. When a ligand binds to a
G protein-coupled receptor (GPCR) that is coupled to a
Gq heterotrimeric G protein, the α-subunit of Gq can
bind to and induce activity in the PLC isozyme PLC-β,
which results in the cleavage of PIP2 into IP3 and DAG.
If a receptor tyrosine kinase (RTK) is involved in
activating the pathway, the isozyme PLC-γ has tyrosine
residues that can become phosphorylated upon activation
of an RTK, and this will activate PLC-γ and allow it to
cleave PIP2 into DAG and IP3. This occurs in cells that
are capable of responding to growth factors such as
insulin, because the growth factors are the ligands
responsible for activating the RTK.
29. IP3 is a soluble molecule and is capable of
diffusing through the cytoplasm to the ER, or the
sarcoplasmic reticulum (SR) in the case of
muscle cells, once it has been produced by the
action of PLC. Once at the ER, IP3 is able to
bind to the IIns(1,4,5)P3 receptor Ins(1,4,5)P3R
on a ligand-gated 𝐶𝑎2+ channel that is found on
the surface of the ER.
The binding of IP3 to Ins(1,4,5)P3R triggers the
opening of the 𝐶𝑎2+
channel, and thus release of
𝐶𝑎2+
into the cytoplasm.
30.
31. DIACYLGLYCEROL
A diglyceride, or diacylglycerol (DAG), is a glyceride
consisting of two fatty acid chains covalently bonded to a
glycerol molecule through ester linkages. Two possible
forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols
32. PROTEIN KINASE C ACTIVATION
In biochemical signaling, diacylglycerol functions as a
second messenger signaling lipid, and is a product of the
hydrolysis of the phospholipid phosphatidylinositol 4,5-
bisphosphate (PIP2) by the enzyme phospholipase C
(PLC) (a membrane-bound enzyme) that, through the
same reaction, produces inositol trisphosphate (IP3).
Although inositol trisphosphate diffuses into the cytosol,
diacylglycerol remains within the plasma membrane, due
to its hydrophobic properties.
IP3 stimulates the release of calcium ions from the
smooth endoplasmic reticulum, whereas DAG is a
physiological activator of protein kinase C (PKC).
membrane.
33. MUNC13 ACTIVATION
Diacylglycerol has been shown to exert some of its
excitatory actions on vesicle release through
interactions with the presynaptic priming protein
family Munc13. Binding of DAG to the C1 domain of
Munc13 increases the fusion competence of
synaptic vesicles resulting in potentiated release.
Diacylglycerol can be mimicked by the tumor-
promoting compounds phorbol esters
34. REFERENCE
Rang and Dale's Pharmacology-James Ritter, Rod J.
Flower, G. Henderson, David J. MacEwan, Yoon Kong
Loke, H. P. Rang
Basic & Clinical Pharmacology- Katzung and Bertram