Intracellular Signalling Flashcards
What events do the the cell signalling result in?
Cell Division Cell growth Diffrentiation Cell Movement Cell Death
Cellular Responses?
- Change in metabolic activities: Glucagon switches liver from synthesising glucagon to breaking it down- BASED ON EXTERNAL ENVIRONMENT
- Changes in gene expression: Epidermal Growth Factor
Activating genes involved in cell growth which can result in the
Change in metabolism - Secret and Release: binding of antigen to mast cell which stimulates the secretion of histamine- BASED ON EXTERNAL ENVIRONMENT
- Sensory Perception: light activation of rhodopsin
What factors act as extracellular Signals
Amino acids- glutamate,adrenaline, dopamine
Steroids- oestradiol, testosterone, cortisol, aldosterone
Gases
Proteins and peptides- glucagon, insulin and growth factor,
prosteoglandins- derived from arachidonic acid
What are the different ways for cells to signal to each other
- endocrine - signals produced by cells in one part of the body travelling in the blood to target cells
- Autocrine- signal acts on the same cell that produces it
- Paracrine- signal that is produced by the cell acts on other cells that are very close
- Neuronal- electrical impulse transmitted down the cell, message passed to another via synapse
- Contact dependant- signal is the integral part of the one cell- directing the signal to another cell. An interaction between 2 cells - Immune system
Describe what receptor are
Cell must express receptor in order to respond to signal
They have high selectivity and high affinity (PROTEINS- HIGHLY SPECIFIC
Signal can bind to different types fo receptor
Alpha adrenergic receptor AND alpha adrenergic receptor both bound by adrenaline but have different functions
Not necessarily on the cell surface
Signal is eventually turned off
Where can receptors be found?
- Cell surface receptor- Hormone is hydrophilic- binding of hormone triggers response inside the cell WITHOUT actually entering the cell
Eg. Adrenaline
-Intracellular Receptor- Hormone is hydrophobic- crosses the plasma membrane. Binding to receptor in the cytosol and triggers a response inside the cell
What are the different types of signalling
ALL COMES DOWN TO BINDING OF RECEPTOR WHICH THEN…
A) Direct activation of enzymatic kinase cascade
Eg EGF-MAP kinase pathway
B) Generation of secondary message inside cell
Eg glucagon- cAMP
C) Depolarisation of the the membrane due to flow of ions
Eg AcH - binding to the nicotinic AcH receptor.
D) Direct activation of transcription factor
Eg Steroid
Steroid hormones contain hormone binding domain, DNA binding domain , domain for interacting with TF
The binding of steroids induces confirmational change which allows for DNA binding and activation of TF genes
What are Secondary Message inside the cell
Can move about into the cell activating different processes- can activate multiple different processes in one cell
Are generated by enzymes
What is GPCR and what is used for?
G protein coupled receptor ( 7 domains)
Activation of adenyl cyclise- converting ATP to cAMP
Activating of phosphorylase-
inositol 1,4,5-triphosphate (IP3)
1,2 Diacylglycerol (DAG)
What are G proteins
they are heterotrimeric complex
Composed of beta, gamma and alpha ( bound to GDP/GTP)
The complex dissociates with GDP is converted from GTP-GDP. This is because there is a confirmational change. This meant the the structure changed which resulted in the function changing. This meant that the complex dissociates
How is adenylyl cyclase stimulated? 1!!!
1) Signal- adrenaline- binds to receptor
2) G protein (GDP bound)associates with receptor
3) GTP/GDP is exchanged on the G protein
4) GDP dissociates into alpha and beta but stays within the membrane
5) Alpha subunits activates effector enzyme
6) Effector ( adenyl cyclase) produces 2nd messenger
7) GTP —> GDP
G-protein complex reassociates
Describe how PKA is formed
When a tetrameric enzyme, 2 regulatory 2 catalytic subunits Approaches cAMP, the Regulatory subunits combine with cAMP- this ensures the tetramer dissociates
Catalytic monomers are now ACTIVE enzymes- PKA
Describe PKA can stimulate transcription
PKA phosphorylase seems CREB
CREB binds to specific sequences in target genes and stimulates transcription
GPCR and IP3/DAG
Some GPCR contain G-alpha subunit
Dissociated Gq activates phosphorylase C
Cleaves inositol phospholipids in membrane- leaving DAG + IP3
IP3 Activates Ca2+ channels in the ER
Increases Ca 2+ concentration in cytosol
The DAG and Ca2+ activates protein kinase
Explain how the enzymatic kinase cascade is activated
EGF binds and triggers the autophosphroylation of Tyr residues in the cytoplasmic domain of receptor. The adaptor proteins contain phosphotyrosine. SOS and Grb2 binds to the receptor. This complex means that GDP-RAS converts to GTP Ras
GTP RAS triggers a kinase cascade.
MAPKKK ——> MAPKK ——> MAPK ——> activates TF
(Mitogen activated protein kinase)
