Sjogren: Lecture 2 Signal transduction 6 GPCR-mediated signaling

Question 1

How does Gq trigger Ca2+ signaling?

Answer 1

Gq effector is Phospholipase CBeta (PLCBeta) which triggers increase in cytosolic Ca2+.

1) PLCBeta hydrolyzes PIP2 to DAG + IP3

2) IP3 (a secondary messenger) gates calcium release through Ca2+ channels from ER

3) Calcium binding to cytosolic proteins alters their functions
- Cytoplasmic Protein Kinase C (PKC) is inactive
- Ca2+ binding promotes PKC binding membranes where DAG is located.

Question 2

What is phospholipid-derived signaling and how does it work?

Answer 2

Receptors such as GPCRs and RTKs lead to activation of phospholipases and phospholipid kinases that Hydrolyze or Phosphorylate various classes of phospholipids.

Lipid phosphorylation and hydrolysis produces 2nd messenger

EX: phospholipase C is membrane associated enzyme that hydrolyzes PIP2

Question 3

What is CaM purpose and function?

Answer 3

Calmodulin (CaM) binds Ca2+ at two terminal domains (EF hands)

Binding causes conformational changes in CaM that expose hydrophobic surfaces.

New CaM conformation binds a variety of cellular signaling proteins.
-EX: Calmodulin-dependent kinases (CaM kinases)
-alters CaM kinase activity including autophosphorylation activity

Question 4

What is important about PIP3?

Answer 4

PI3-kinases turn PIP2 into PIP3.

This secondary messenger is a docking site in the membrane to trigger various cascades.

Question 5

What are signaling pathways?

Answer 5

They are integrated

Not exclusive or independent.