Cell Signalling 3 Flashcards
Receptors are present in both cell surface or within a cell. What are the general property of the signal for both types of receptors
Cell surface receptors are often coupled with hydrophilic signals - which can’t cross plasma membrane
Intracellular receptors are often coupled with hydrophobic - which are able to cross the plasma membrane
What are the two general ways ( reaction ) that is used for signallling ?
Generally, signalling can occur by phosphorylation and through GTP-binding proteins
Both are basically by phosphorylation - by ATP and GTP
How are heterotrimeric G-proteins activated ?
Heterotrimeric G-proteins are activated by ligands binding to GPCRs ( G protein coupled receptors )
Give the diferent types of alpha subunits of G-proteins and their function ( what do they produce )
alpha-s - activates adenylyl cyclase which upregulates the production of c AMP
alpha-i - deactivates adenylyl cyclase which downregulates the production of c AMP
alpha q - activates Phospholipase C-Beta which upregulates production of IP3 and DAG
What does c AMP activate what does this then result in?
How is cAMP degraded ?
cAMP activates PKA which then phosphorylates target proteins
cAMP is degraded by phosphodiesterases ( converts cAMP into 5’-AMP)
The alpha-q subunit of a G-protein activates Phospholipase C-Beta
What secondary messengers are produced by Phospholipase C-Beta ?
Phospholipase C-Beta produces secondary messengers IP3 and DAG
What does IP3 activate ?
IP3 activates intracellular ligand-gated calcium ion channels - resulting in the release of Ca2+ ions
IP3 causes the release of Calcium ions - what regulates the effects of Calcium ions and how ? ( what do calcium ions activate ) - given an example to what it can activate further
Calmodullin is activated by Ca2+ ions -it wraps around a target protein - and activate protein kinases such as CamII( Calmodullin dependent protein kinase)
How does CAMII become activated (what is its structure) - describe a way in which it can be further activated
CAMii is a complex made out of a catalytic domain + ( Ca2+/Calmodullin)
CAMII- is then further activated by phosphorylation by ATP
Calcium takes part in activating CAMII- describe ways in which calciums effects are reduced
Calciums effects can be reduced by taking it away -
PMCA and SERCA (both ATPases) and NCX ( exchanger )
the actions of these protein channels and exchangers bring calcium levels to an inactive level
DAG’s effects are mediated by protein kinase C - decribe the Ca2+-DAG “conspiracy”
IP3 brings Ca2+ levels to an “active” concentration
Ca2+ binds to PKC ( Phospokinase C ) -
This complex is then translocated to the PM where it can bind to DAG
The enzyme complex is then activated to phosphorylate substrates
Describe the structure of enzyme linked receptors and why they work relatively fast -
It contains two transmembrane regions- receptor domain and enzyme domain
Enzyme linked receptors when stimulated activate the enzyme domain directly - resulting in relatively fast effects
there are two types of tyrosine kinases but what are their general properties and how they work ?
Tyrosine kinases - dimerize (form two subunits ) and autophosphorylate ( phosphate from one subunit transferred to another )
They then recruit other proteins which result in a cellular response
MAP kinase signalling pathway is triggered by tyrosine kinase - describe this pathway from stimulus to cellular response )
- Receptor tyrosine kinase activated by growth hormone EX . FGF
- Results in recruitment of proteins to transduce the signal …Grb2 recruit other proteins to tyr kinase , SOS activate 3rd protein , Ras to activate monomeric G protein
- MAP kinase phosphorylation occurs , MAPKKK, MAPKK, MAPK
- Effectors activated
- Overall cellular response is produced - FGF results in the mesodermal induction during early developmental stages
