Shemanko Lecture 7

Question 1

What is the generic function of G-proteins?

Answer 1

To help activate effector molecules which then make second messengers

Question 2

When are G proteins inactive?

Answer 2

When they’re GDP bound

Question 3

When are G proteins active?

Answer 3

When they’re GTP bound

Question 4

How do G proteins become inactive?

Answer 4

Through hydrolysis

Question 5

How do G-protein coupled receptors and heterotrimeric G proteins work together?

Answer 5

The heterotrimeric G protein relays signal to an effector molecule through binding to the G protein coupled receptor which then relays it to the nucleus

Question 6

What is the structure of the G protein?

Answer 6

Has alpha, beta, and gamma subunits, alpha and gamma subunits are linked to membrane via a lipid group.

Question 7

Describe the receptor mediated activation of effectors by heterotrimeric G proteins?

Answer 7

1. The ligand binds to the receptor, this alters the confirmation of the receptor and that causes G protein to bind to the receptor.
2. The GTP binding site (alpha unit) on the G protein releases GDP for GTP via nucelotide exchnage
3. The Ga subunit of the G protein chnages confirmation and binds to effector (adenyl cyclase)
4. The effector produces cAMP (second messenger)
5. The Ga subunit gets hydrolyzed, GTp turns back to GDP, gets inactivated
6. Ga subunit cmes of effector and goes back to rest of g protein, makes inactive heterotrimeric g protein
7. The receptor becomes phosphorylated by G protein kinase (GRK)
8. Arrestin binds to the phosphorylated receptor which turns it off, the receptor gets endocytosed and arrestin degrades other second messengers

Question 8

What produces cAMP?

Answer 8

adenylyl cycalse (effector) is a integral membrane protein whos domain resides at the inside of the plasma membrane -> makes cAMP from ATP

Question 9

What is cAMP broken down by? Why?

Answer 9

phosphodiesterase, so it doesn’t overstimulate the cell

Question 10

Why did we do an experiment where we put three cell signals (ACTH, glucagon, and epinephrine) activate differently?

Answer 10

To see whether adenylyl cyclase activity increased proportionally, found it didn’t cause the effector adenylyl cyclase is share dby receptors.

Question 11

How does a liver cell respond to glucagon and ephnepherine ((cell signal) (glucose pathway)?

Answer 11

Ligand and receptor bind. THE g protein gets activated via GDP to GTP, binds to effector (adenyl cycalse), effector produces cAMP, cAMP activates protein kinase A, this then breaks glycogen into sugars, activates glycogen synthase, and goes to nucelus and turn on genes that help produce glucose by phosphorylating CREB which binds to CRE (in DNA)

Question 12

What pathway do CRE’s encode?

Answer 12

gluconeogenesis (a pathway by which glucose is formed from glycolysis)

Question 13

What does the cell signal epinepherine do for skeletal muscles? What does it do for cardiac muscle?

Answer 13

breaks down glycogen, inhibits glycogen synthesis.
increased contractility