Question

In: Biology

Describe how activation or synthesis occurs in the follow steps in the GPCR signaling pathway. GPCR...

Describe how activation or synthesis occurs in the follow steps in the GPCR signaling pathway. GPCR and G protein signal molecule and GPCR protein kinase A and cAMP protein kinase A and other protein kinases adenylyl cyclase and cAMP

Solutions

Expert Solution

G protein coupled receptors (GPCR) are important players in cell signaling. GPCR GPCR signaling operates principally by two pathways-

i.cAMP signaling

ii Phosphatidylinositol (calcium) mediated pathway

Here, We will be focussing on the first one.

GPCR triggers it's effect after being bound by any agonist. Once GPCR is activated the guanine exchange factor (GEF) domain undergoes conformational change and facilitates replacement of GDP with GTP and turns on the signaling cascade.

the first thing to happen is activation of bound G protein due to conformational changes. G protein is trimeric protein with three subunits (alpha, beta , gamma).

When GPCR is activated alpha(s) is detached from beta and gamma. and this free alpha subunit binds with GTP .it is deactivated when GTP is converted to GDP). This signaling cascade can be terminated by hydrolysis of GTP of alpha sububit to GDP (alpha subunit has intrinsic GTPase activity with help of several GAP proteins). When alpha subunit binds with GDP it again reorganizes with beta and gamma subunits of G protein and waits for another activation cycle.

G alpha subunit-GTP then binds and activates Adenylate cyclase.

Adynylate cyclase converts ATP to cAMP. c AMP

c AMP then binds with regulatory subunit of protein kinase A and activates it (Protein kinase A is a heterotetrameric protein.2 regulatory and 32 catalytic subunits are present.)

When c AMP binds regulatory subunit- it releases the catalytic subunit.

The catalytic subunit is now free to phosphorylate several target proteins on serine or threonine residues and activates them.

In short

Activated G protein--G apha subunit with bound GTP---Activates Adenylate cyclase--c AMP is produced--cAMP activates protein kinase A

This signaling cascade can be terminated by by the action of phosphodiesterases (It converts cAMP to 5'AMP).


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