Cell signalling Flashcards
What can cell signalling cause?
Cell division Cell growth Differentiation Cell movement Cell death
What are the cellular responses to signalling + examples
Change in metabolic activity - glucagon switches liver from synthesising glycogen to metabolising
Secreting/release - binding of antigen causes mast cells to secrete histamine
Changed gene expression - epidermal growth factor (EGF) activates genes involved in cell growth
Sensory perception - light activation of rhodopsin
What can act as extracellular signals + examples?
Amino acids + derivatives = glutamate, adrenaline, dopamine
Steroids = oestradiol, testosterone, cortisol, aldosterone
Prostaglandins (eicosanoids, derived from arachadonic acid)
Proteins + peptides = insulin , glucagon, growth factors EGF
Gases = NO, CO
What amino acids + derivatives can act as extracellular signals?
Glutamate
Adrenaline
Dopamine
What steroids can act as extracellular signals?
Oestradiol
Testosterone
Cortisone
Aldosterone
What are prostaglandins?
Eicosanoids, derivatives of arachadonic acid.
What proteins/peptides can act as extracellular signals?
Insulin, glucagon, growth factors, EGF
What gases can act as extracellular signals?
NO, CO
What are they ways in which cells can signal each other?
Paracrine Autocrine Contact-dependent Endocrine Neuronal (PACEN)
What is paracrine signalling
Signal produced by cell close by
What is autocrine signalling
Signal produced by cell itself
What is endocrine signalling
Signal produced in one part of the body, and then travels in the blood and acts elsewhere
What is contact dependent signalling
Signal is integral part of one cell which interacts directly with another cell
What is neuronal signalling
Electrical signal sent down a cell, passed on via synapse
What are the two types of receptor and what type of signalling substances do they respond to?
Cell surface receptor - hydrophilic substances such as adrenaline. The signalling hormone does not enter the cell.
Intracellular receptor - hydrophobic substances such as steroid hormones. Hormone crosses the membrane and enters cytosol to trigger a response inside the cell.
What can signalling cause within a cell
Depolarisation of membrane due to the flow of ions (acetlycholine)
Direct activation of transcription factor (steroid)
Production of secondary messenger (cAMP)
Direct activation of enzymatic kinase cascade (EGF - MAPkinase pathway)
Example of signalling causing depolarisation of membrane due to flow of ions
Acetylcholine binding to nicotinic acetylchloline receptor
Example of signalling causing the direct activation of transcription factors
Binding of steroid induces a conformational change which allows DNA binding + activation of transcription of target genes.
Examples of secondary messengers
cAMP cGMP Ca2+ IP3 DAG
IP3
Inositol-1,4,5-trisphosphate
DAG
Diacylglycerol
What does GPCR stand for?
G-protein coupled receptor
Give an example of a GPCR
Beta-adrenergic receptor
How can stimulation of the Beta-adrenergic receptor lead to the production of cAMP?
Stimulation of GPCR B-adrenergic receptor by adrenaline activates a G-protein.
The as subunit swaps GDP for GTP then dissociates from beta and gamma units to activate the adenylyl cyclase; which produces cAMP.
GTP hydrolysed to GDP as as-b-y complex re-associates, signalling ends.
How does cAMP activate PKA
Inactive PKA (protein kinase A) is made up of 4 monomers: 2 regulatory subunits and 2 catalytic subunits. 2 molecules of cAMP bind to the regulatory subunits and releases the catalytic subunits, activating it.
How can cAMP affect gene transcription?
It activates CREB (cAMP response element binding protein); which binds to specific genes, stimulates transcription
Then long term adaptation to starvation to change in gene expression.
What is CREB
cAMP response element binding protein
How can GPCR be involved with IP3 and DAG in activation of PKC
GPCR (in alpha1-adrenergic receptors) can have a G-alpha-q / Gq subunit; which activates phospholipase C
Phospholipase C cleaves inositol phospholipids- producing inositol-1,4,5-trisphosphate and diacylglycerol. IP3 activates Ca2+ channel in ER and so increases cytoplasmic [Ca2+], this alongside DAG can activate PKC.
What is RTK
Receptor tyrosine kinase
What does RTK do
Causes direct activation of enzymatic kinase cascade without a secondary messenger.
Binding of EGF triggers autophosphorylation of tyrosine residues in cytoplasmic domain of receptor.
Activates exchange of GDP-Ras to GTP-Ras
Ras is a G-protein that triggers a kinase cascade
What does Ras do
Its a G-protein that triggers a kinase cascade;
MAPKKK-MAPKK-MAPk-transcription factor
(mitogen activated protein kinase …)
No secondary messenger
What is convergence in terms of intracellular signalling?
When two different signals cause the same effect in a cell
What is crosstalk in terms of intracellular signalling?
When two signals block each other (dimmer switch analogy)