Topic 5: G-protein independent signalling Flashcards
What is homologous desensitisation?
where the attenuation of the cellular response is specific to the receptor being stimulated.
what is hetrogous desesnsitaisation?
where receptors not stimulated by the agonist are also desensitised.
what is one receptor level of desensitisation- what is its mechanism of action?
phosprsalation of the receptor following stimulation on multiple sites usually on the C terminal or third intercellular loop of the GPCR.
what are the fatures of heterologous receptor phosphoralation?
mediated by PKA/PKC
both agonist occupied and unoccupied receptors are effected.
slow but can occur at low receptor occupation due to receptor reserve.
steps in homologus receptor desintisation
activation - g protein signalling
phoshoralation by GRKs (BARK ect)
arrestin protein binds - selective to receptor
steps in receptor internalisation
arssestin already bound
acts as a scaffolding protein for claterin and clatherin adaptor protein AP2
forms a catherin coated pit
dynamin pinches off vesicle.
what happens to a GPCR after it is internalised check
acidified vesicle causes unbinding of arrestin and phospatasation
then receptor is resesnsitised
or degraded.
what is a GRK
G-protein coupled receptor kinase
there are 7 in total
what GRKs phosparalate b receptors
GRK2 - B-ARK1
GRK3 - B-ARK2
what do the diffrent parts of the non visual GRKs do?
RH domain - Ga interaction - GRK 4,5,6 dont have this
calylictic doin- ATP and protein binding
PH- membrane and recetly activated recptor bindig
how is GRK2/3 recruited to the ligand occupied receptor?
via Gby and PIP2 and GRK2/3 RGS like domins will seqester Ga subunits
give an example of how GPCR-arrestin complexes can act as a signalling cascade
can act as scaffolding proteins, and requit non RTK Src which cam them actovatr MAPK signnaling
What are biased ligands
they can select between the two forms of GPCR signalling
dependent or independent.
what may determine cell specific receptor arresting signalling?
conformation of arresting might be determined by phosphyration signature
active conformation might determine which signalling pathways the protein scaffolds with
this might contribute to receptor specific g-protein independent signalling
does arrestin binding always and internaltion always lead to G-protein dependent signalling cessation?
there is evidence that they migh comtiue to signnal g protein depndently, and that they could formGPCR megaplexes.
