Signalling via Heterotrimeric G-Proteins

Question 1

What are the TWO major groups of Signalling G-Proteins?

Answer 1

1. Monomeric Ras G-protein
2. Heterotrimeric G-protein

Question 2

Which G-proteins do signalling molecules act via to increase the levels of secondary messengers?

Answer 2

Heterotrimeric G-proteins

Question 3

What is the mechanism of action for signalling via G-proteins?

Answer 3

1. G-protein binds GTP or GDP
2. Transduce hormone / neurotransmitter signals
3. G-proteins couple signals to secondary messengers

Question 4

How is GTP converted to GDP on G-proteins?

Answer 4

By hydrolysis of the gamma phosphate of GTP

Question 5

What is the mechanism of action of signal transduction via heterotrimeric G-proteins?

Answer 5

1. Hormone binding causes conformational change in receptor
2. Receptor binds α subunit of G-protein (GDP bound state)
3. Binding of receptor causes conformational change in α subunit (GTP replaces GDP)
4. α dissociates from β and γ and binds adenylyl cyclase
5. Synthesis of cAMP activated
6. Hormone dissociates
7. GTP hydrolysed to GDP
8. α binds β and γ again

Question 6

What is the function of Gαs?

Answer 6

Alpha subunit which activates adenylyl cyclase

Question 7

How many isoforms of Gαs are there?

Answer 7

3

Question 8

Which ligands activate Gαs?

Answer 8

Stimulatory ligands such as Adrenaline and Glucagon

Question 9

What is the function of Gαi?

Answer 9

Prevents adenylyl cyclase activation

Question 10

Which ligands activate Gαi?

Answer 10

Activated by inhibitory ligands such as Adenosine

Question 11

How many members does Gαi contain?

Answer 11

At least 9

Question 12

What is the function of Gαq?

Answer 12

Activate phospholipase C that increases DAG and IP3

Question 13

How many isoforms does Gαq have?

Answer 13

5

Question 14

How many members does Gα12 have?

Answer 14

2

Question 15

TRUE OR FALSE:
Different Gα subunits couple different GPCRs

Answer 15

True

Question 16

What is the function of the secondary messenger cAMP in the G-protein signalling pathway?

Answer 16

Activates Protein Kinase A (PKA)

Question 17

What is the function of the secondary messenger cGMP in the G-protein signalling pathway?

Answer 17

Activates Protein Kinase G (PKG) and opens cation channels in rod cells

Question 18

What is the function of the secondary messenger DAG in the G-protein signalling pathway?

Answer 18

Activates Protein Kinase C (PKC)

Question 19

What is the function of the secondary messenger IP3 in the G-protein signalling pathway?

Answer 19

Opens Ca2+ channels in the ER

Question 21

TRUE OR FALSE:
The Gα subunit does not have GTPase activity

Answer 21

False.
Gα subunit HAS intrinsic GTPase activity which allows the hydrolysis of GTP to GDP

Question 22

What TWO ways can G-protein coupled responses be decreased by desensitisation?

Answer 22

• Receptor internalisation
• Phosphorylation of the receptor by GCPR kinases (GRKs)

Question 23

How does Cholera toxin affect Gαs G-proteins?

Answer 23

• Irreversibly activates Gαs G-proteins by ADP-ribosylation
• Leads to an excessive, non-regulated elevation in cellular cAMP levels

Question 24

How does Pertussis toxin affect Gαi G-proteins?

Answer 24

• ADP-ribosylates Gαi
• Permanently locks G-protein into the GDP-bound state (removes inhibitory action)
• Leads to an increase in cAMP levels

Question 25

What is the function of the βγ subunits of G-proteins?

Answer 25

Regulate plasma membrane K+ channels