Signaling-2

Question 1

Mutations of…..are common in human tumors

Answer 1

Ras protein family

Question 2

Alpha sunbuit is bound to…..in resting state and has intrinsic…..activity.

Answer 2

GDP
GTPase activity

Question 3

Gq activates……

Answer 3

Phospholipase C

Question 4

Describe the cascade of G-coupled protein using cAMP as 2nd messenger

Answer 4

1. The binding of hormone to receptor triggers condormational change which causes activation of G-protein
2. Active G-protein dissociates from occupied receptor and replaces GDP with GTP and alpha dissocites from b&g
3. GTP loaded Ga bind to adenyl cyclase activating it (Gas)
4. Increase cAMP
5. cAMP binds regulatory subunits of protein kinase A (R2C2) freeing the catalytic subuits which can phosphrylate target proteins and produce cellular effects

Question 5

Describe effect of cAMP on transcription

Answer 5

It is mediated by CREB which can be phosphorylated by protein kinase A so it can bind with CBP and becomes a very potent transcription factor.

Question 6

Describe termination of hormonal action

Answer 6

1. Stimulation of AC is terminated as GDP is cleaved to GTP by intrinsic GTPase activity of a sunbuit, which then associteds with b and g subunit ready to respond to new signal.
2. cAMP is broken down by PDE
3. Phosphatases cleave phosphate group from proteins thus terminating its action

Question 7

Mention hormones with receptors having:
1. Gs
2. Gi

Answer 7

1. Beta of CAs, glucagon, ACTH, FSH, LH, TSH
2. Somatostatin and a2 of CAs

Question 8

Describe effect on signal transduction of:
1. Cholera t.
2. Pertusssis toxin

Answer 8

1. ADP-ribosylation of Gas blocking is GTPase activity causing its continuous activation and activation of AC producing level of cAMP causing constant secretion of Cl, HCO3 and water.
2. ADP ribosylation of Gai preventing displacement of GDP by GTP so blocking activation and causing rise of cAMP

Question 9

Action of cGMP are mediated by…..

Answer 9

Protein kinase G

Question 10

Atrial natriureric factor receptor is…..while that of nitric oxide is……and associated with……

Answer 10

Membrane spanning guanylyl cyclase
Soluble cytosolic guanylyl cyclase
Heme group

Question 11

Describe mechanism of action of Sildenafil

Answer 11

Inhibit cGMP PDE which regulated blood flow to penis causing prolonged VD and erection.