24_Signal Transduction II

Question 1

G-proteins exist in two states: active GTP-bound and inactive GDP-bound.
What facilitates the interconversion of these two states? (i.e. hydrolysis vs. exchange)

Answer 1

active (GTP) –> inactive (GDP): hydrolysis

inactive (GDP) –> active (GTP) exchange

Question 2

There are loops on either side of a transmembrane GPCR. Which end of these loops (N/C) do the ligand and G-protein bind to?

Answer 2

ligand binds to N-terminal loops outside cells

G-protein binds C-terminal loops inside cells

Question 3

Which subunits of a heterotrimeric G-protein are anchored to the plasma membrane using lipid groups?

Answer 3

α and γ

Question 4

Which subunit of a heterotrimeric G-protein binds to the effector?

Answer 4

α

Question 5

Which heterotrimeric G-protein subunit has intrinsic GTP-ase activity?

Answer 5

α

Question 6

Ligand binding induces a conformational ∆ in the GPCR, which activates G-proteins. This conformational ∆ also makes the GPCR an attractive substrate for another protein. Which protein is this, and what are the consequences of its action?

Answer 6

The GPCR becomes a good substrate for GRK (GPCR-kinase). It phosphorylates the GPCR, allowing binding of arrestin. Arresting competes with G-proteins for the receptor.

ultimately => termination of response

Question 7

How is the Gα subunit signal terminated? (effect specific to the subunit – so NOT arresting binding to GPCR)

Answer 7

hydrolysis of GTP to GDP

Question 8

In glucose mobilization, what is the effector molecule? What about the 2nd messenger?

Answer 8

effector: adenylyl cyclase

2nd messenger: cAMP

Question 9

How are the actions of glucagon and insulin related?

Answer 9

they have essentially “opposite” fx

glucagon: simulates glycogen breakdown & glucose mobilization
insulin: stimulates glycogen storage & glucose uptake

Question 10

What is an example of a ligand that acts in a manner similar to glucagon in terms of stimulating glycogen breakdown?

Answer 10

epinephrine

Question 11

Which enzyme catalyzes conversion of cAMP to AMP through ring breaking?

Answer 11

phosphodiesterase

Question 12

PKA phosphorylates ______ within the nucleus.

Answer 12

CREB

Question 13

In glucose mobilization, how does phosphorylase kinase get activated? Once activated, what does it do?

Answer 13

it is activated through phosphorylation by PKA

it then goes on to phosphorylate and activate glycogen phosphorylase, which catalyzes the RDS in glycogen hydrolysis

Question 14

Which enzyme in the glucose mobilization pathway is inactivated through phosphorylation?

Answer 14

Glycogen synthase

Question 15

How does cAMP amplify the GPCR response within the cell?

Answer 15

activation of many PKA molecules