PIP2 PLC

Question 1

What is the significance Phospholipase C-βs?

Answer 1

PLC-βs are important effectors of G protein-coupled receptor (GPCR)-mediated signaling pathways including those stimulated by the neurotransmitters acetylcholine and bradykinin

Question 2

What do PLC-βs do in GPCR pathways?

Answer 2

hydrolyze PIP2, itself a signaling molecule, to form two other second messengers, diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3)

Question 3

What are PLC-βs stimulated by?

Answer 3

Gα subunits of the Gq family, by Gβγ subunits of the Gis, and, in the case of PLC-β2, by Rac.

Question 4

How does PLC-β hydrolyse PIP2?

Answer 4

1. PLC pleckstrin homology (PH) domain encounters a PIP2 in the plasma membrane
2. it binds to PIP2 with sufficiently high affinity and specificity to anchor the protein to the membrane.
3. This confines the catalytic site of PLCδ to the surface phase. In the surface phase, the catalytic site experiences a ≈1000-fold higher concentration of PIP2 than if it was diffusing throughout the cytoplasm of a cell,
4. which greatly facilitates PLCδ’s ability to hydrolyze PIP2 when it is activated by an increase in intracellular Ca2+

Question 5

What does PIP2 hydrolysis lead to?

Answer 5

PIP2 is hydrolysed into IP3 and DAG and the consequences of this hydrolysis are calcium release, PKC activation, net PIP2 depletion and channel inhibition

Question 6

How is PKC activated?

Answer 6

PKC is activated through DAG binding to a conserved C1 domain in PKC in a Ca2+ dependent manner which

Question 7

What are the effects of DAG binding to PKC>

Answer 7

alongside activation, leads to the plasma membrane translocation

Question 8

What is PKC?

Answer 8

PKC belongs to a family of ten serine/threonine kinases that are classified into three subfamilies based on their ligand and cofactor requirements

Question 9

What does PKC do?

Answer 9

relays information in the form of a variety of extracellular signals across the membrane to regulate many Ca2+-dependent processes.

Question 10

What are the implications of PKC activation on muAchR’s and BK receptors?

Answer 10

activation of these receptors triggers IP3 dependent calcium waves that are crucial to smooth muscle contraction and response to tissue injury through PKC activation.