Signal transduction

Question 1

What is the pathway for signal transduction through Ga(s) GCPRs?

Answer 1

agonist binds with GPCR -> activates GEF to switch GDP into GTP in GasBy (g-protein) -> separates into Gas-GTP and GBy -> Gas-GTP stimulates anedylyl cyclase -> increases cellular cAMP -> stimulates phosphorylation of target proteins via cAMP - dependent kinase (PKA).

Question 2

What is the pathway for signal transduction through Ga(i/o)

GCPRs?

Answer 2

inhibits adenylyl cyclase -> decreases cellular cAMP -> decreases cellular cAMP responses

Question 3

What is the pathway for signal transduction through Ga(q)

GCPRs?

Answer 3

agonist binds to GCPR -> Ga(q)By splits after GDP is exchanged for GTP -> Ga(q)-GTP activates phospholipase C (PLC) -> PLC cleaves PIP2 (membrane phospholipid), generating the second messengers IP3 and diaglycerol

Question 4

What does DAG (diaglycerol) do once it is created in the Gq pathway?

Answer 4

It recruits and activates protein kinase C, which then phosphorylates specific target proteins on hydroxyls of serine and threonine residues

Question 5

What is IP3 and what does IP3 do once it is created in the Gq pathway?

Answer 5

IP3 is a ligand for a calcium ion channel (IP3 receptor) on the endoplasmic reticulum -> it opens and Ca2+ flow from ER into cytoplasm, triggering Ca2+ sensitive processes

Question 6

How is GCPR signaling terminated?

Answer 6

activated receptors are recognized and phosphorylated by G-protein coupled receptor kinases (GRKs) -> Phosphorylated receptors may have reduced activity, and they can be turned off fully by binding of arrestins at the plasma membrane -> Signaling stops -> arrestin-GCPR may be endocytosed via cathrin-mediated endocytosis.

OR via Ga-GTP hydrolysis to Ga-GDP via GTP hydrolysis carried out by Ga subunit itself, which has GTPase activity.

Question 7

Can agonists act on more than one G-protein?

Answer 7

Yes - new G-proteins bind until agonist is no longer present.

Question 8

What enzyme turns off cAMP singaling?

Answer 8

PDE (phosphodiesterase) - cleaves cAMP into AMP

Question 9

What is the Akt signaling pathway?

Answer 9

self-phosphorylates - P-sites become protein binding sites -> IRS-1 binds and is phosphorylated by the receptor -> binds to PI3K -> phosphorylates PDK1 -> PDK1 phosphorylates and activates Akt -> ??????

Question 10

How do steroid hormones bind?

Answer 10

Bind to DNA as dimers @ hormone response elements.

Question 11

How do steroid hormones cause effect?

Answer 11

After they bind to the DNA a complex assembles that brings RNA polymerase and increasing transcription.