G Protein Mediated Signalling II

Question 1

GPCR-Gα Selectivity and Coupling

Answer 1

somatostatin inhibits insulin release
- needs Gαo2 (specific subunit)

GPCRs do not share G proteins – discrete pathways

Question 2

AKAPs

Answer 2

• bring substrates in close proximity
• contains subcellular targeting domain (restrict location)

Question 3

AKAP79

Answer 3

Associates with β2-andrenergic receptor (cAMP/PKA)
- desensitaztion of receptor
- enhance glutamate receptor

Question 4

Negative Feedback Loop by mAKP

Answer 4

Resting
- PKA inactive, PDE breaks down cAMP
Hormonal Stimulation
- cAMP increase, activate PKA, phosphorylate substrates
Feedback Inhibition
- PKA phosphorylates PDE –> break down cAMP = less PKA activity

Question 5

PDZ Domain

Answer 5

• recruit and interact proteins
• formation of signalling networks
• some can bind to GPCRs

Question 6

INAD Signalling Complex

Answer 6

binds to multiple signalling proteins
- proximity to increase signalling efficiency
- contain 5 PDZ domains

Question 7

GIPC binds to…

Answer 7

RGS19 and D2/D3 dopamine receptors
- GIPC has a PDZ domain
- D2 receptor = RGS19 needs GIPC to form a complex with receptor and G-protein to limit agonist signal

Question 8

Other RGS Scaffolding Protein

Answer 8

Spinophilin
- targets RGS2 to α1B adrenergic receptor
- increase ability RGS2 to inactivate G-protein

Question 9

PM Microdomains

Answer 9

Lipid Rafts – coalescence of sphingolipid + cholesterol
Caveolae – indentations of PM (lipid + caveolin)
– certain receptors localize here = selectivity