Week 3 GPCRs/RTKs and Steroid Hormones

Question 1

Describe the G-alpha-S pathway

Answer 1

Stimulates adenylyl cyclase which converts ATP to cAMP (2nd messenger) to activate PKA (protein kinase) to phosphoralate hydroxyl groups of target proteins

Question 2

Describe the G-alpha-I pathway

Answer 2

Inhibits (decrases) cAMP

Question 3

Describe the G-alpha-Q pathway

Answer 3

Recruits PLC (phospholipase C) to cleave PIP2 which can activate two pathways:

1) DAG to activate PKC to phosphorylate target protein
2) IP3 a ligand for IP3 receptor at ER resulting in outflow of Ca2+

Question 4

How is GPCR terminated?

Answer 4

1. On G-alpha, GTP –> GDP
2. G-alpha-GDP dissociates from adenylyl cyclase
3. G-alpha-GDP binds to beta-gamma
4. Deactivated adenylyl cyclase halts cAMP production
5. Phosphodiesterase destroys remaining cAMP via dephosphorylation
6. PKA stops phosphorylation
7. Remaining proteins are dephosphorylated
   Can also be terminated by ARRESTIN that can bind to PCR which internalizes and removes GPCR from membrane preventing GRK + ATP from phosphroylating it.

Question 5

Describe the structure and function of RTKs (receptor tyrosine kinase)

Answer 5

RTK is a dimer or forms a dimer that span the plasma membrane allowing ligand to reach external receptor to set off internal activity. The dimers can “autophosphroylate” each other.
RTK’s function: to set off a signalling cascade within the cellular environment.

Question 6

What is convergence?

Answer 6

Occurs when two different receptors activate the same secondary messenger which leads down the same pathway.

Question 7

What is crosstalk?

Answer 7

Occurs when an GPCR ligand must cleave an RTK ligand before the RTK ligand can bind to the RTK to activate it.

Question 8

Describe steroid hormone receptors (SHR)

Answer 8

1. Part of the nuclear hormone receptor family
2. SHR’s have many ligands are that are structurally and functionally different.
3. All SHR ligands are hydrophobic and easily pass through the plasma membrane
4. SHRs are located INSIDE of the cell.
5. They are homodimers.

Question 9

Describe the steroid hormone receptor (SHR) activity.

Answer 9

1. Remember: Not part of the membrane.
2. Acts as a transcription factor to regulate the expression of specific genes: Steroid/receptros binding causes increased affinity of receptor to short DNA sequence which then activates transcription
3. Can be bound to short DNA sequence (without steroid) which prevents transcription until steroid binds to receptor.