G-protein signaling

Question 1

What is a first messenger?

Answer 1

Intercellular signaling molecules secreted by signaling cells.

Question 2

What is a receptor?

Answer 2

A specific recognition site of the ligand/hormone.

Question 3

What are the 5 things that can happen when a ligand binds a receptor?

Answer 3

1. Change in conformation
2. Aggregation of ligand bound receptors.
3. Generation of enzymatic activity
4. Exposure of binding site for other molecules
5. Coupling of activated receptor to the activation of other molecules/enzymes.

Question 4

Describe the steps to G-protein activation.

Answer 4

1. GTPase binds and hydrolyzes GTP

2. Binding of GTP to G-protein activates it and transfers signal downstream.

Question 5

Describe the G-protein.

Answer 5

Has 3 subunits,

1. Alpha: has GDP bound but exchanges it for GTP when bound to activated receptor
2. Beta
3. Gamma

Question 6

What happens to the G-protein alpha subunit when GTP is bound?

Answer 6

It dissociates from the beta and gamma subunit and activates adenylyl cyclase.

Question 7

What are the 3 ways this system can turn itself off?

Answer 7

1. Ligand can dissociate from receptor
2. GTP hydrolyzed to GDP
3. Dissociation of the alpha subunit of G-protein.

Question 8

What is the role of Adenylyl Cyclase?

Answer 8

Turns ATP into cAMP

Question 9

What is the role of Protein kinase A/A kinase?

Answer 9

It binds cAMP; Has 4 subunits. 2 regulatory and 2 catalytic. The binding of cAMP dissociates the subunits

Question 10

What does the catalytic subunits of Protein kinase A do once they’re dissociated from the regulatory subunits?

Answer 10

It transfers a phosphate from ATP to a target protein(Ser/Thr residues), activating it.

Question 11

What is the cAMP turn off signal?

Answer 11

Its conversion into AMP by cAMP phosphodiesterase

Question 12

Discuss the conservation of parts

Answer 12

The same proteins are used in second messenger systems in different cells; Triggering different events.

Question 13

What are some important receptors coupled through Gi protein?

Answer 13

1. A2 adrenergic receptors: Normal ligand is norepinephrine or epinephrine
2. M2 muscarinic cholinergic receptors: Normal ligand is Ach
3. Some cells have both Gs and Gi receptors; Allows tighter control over adenylate cyclase.

Question 14

Discuss the Phospholipase C pathway.

Answer 14

1. Agonist binds to receptor and activates it
2. Gq is activated, then activates Phospholipase C beta.
3. Phospholipase C beta cleaves PIP2, making IP3 and DAG

Question 15

Describe Phosplipase C beta

Answer 15

A membrane bound enzyme that cleaves PIP2 into IP3 and DAG.

Question 16

Describe IP3

Answer 16

A second messenger that leaves the membrane and enters cytosol; Activates IP3 receptors on SR

Question 17

Describe DAG

Answer 17

A second messenger that stays bound to the CM; Activates protein kinase C, which then activates target proteins.

Question 18

Discuss the action on the SR once calcium is in the cell.

Answer 18

Calcium binds to calmodulin, which binds and activates a calcium-calmodulin dependent protein kinase/