IP3 PLC + PKA

Question 1

What do heterotrimeric G proteins consist of?

Answer 1

α, β, and γ subunits that are stably associated in the inactive, GDP-bound state

Question 2

How do G proteins dissociate?

Answer 2

Physical interaction between a G protein and an agonist-occupied receptor triggers the exchange of GDP for GTP on the α subunit and the subsequent dissociation of this subunit from the tightly associated βγ dimer

Question 3

What underlies GPCR intracellular signalling?

Answer 3

Both the Gα-GTP and Gβγ entities participate in intracellular signalling

Question 4

How is GPCR signalling inactivated?

Answer 4

The intrinsic GTPase activity of the Gα subunit mediates the rate-limiting hydrolysis of GTP to GDP and results in the reassociation of this subunit with the Gβγ complex and consequent inactivation of signalling.

Question 5

Which alpha subunits of which G protein family activate PLC?

Answer 5

The α subunits (αq, α11, α14, and α16) of all four members of the Gq subfamily activate PLC-β isozymes

Question 6

How does activated Gαq activate PLC?

Answer 6

interacts with the COOH-terminal region of PLC-β1 downstream of the Y domain; this region contains the C2 domain (residues 663–802) followed by a sequence (residues 803–1216) that is unique to this subfamily of PLC isozymes

Question 7

How does PLC hydrolyze PIP2?

Answer 7

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. confines the catalytic site of PLCδ to the surface phase
4. 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

Question 8

Why is it important that PLCδ

moves to the surface phase?

Answer 8

Facilitates PLCδ’s ability to hydrolyze PIP2 when it is activated by an increase in intracellular Ca2+

Question 9

PIP2 is hydrolyzed to:

Answer 9

IP3 and DAG

Question 10

Consequences of PIP2 hydrolysis

Answer 10

1. Calcium release
2. PKC activation
3. Net PIP2 depletion
4. Channel Inhibition

Question 11

How is PKC activated?

Answer 11

DAG binding to a conserved C1 domain in PKC in a Ca2+ dependent manner

Question 12

Downstream effect of DAG binding to PKC

Answer 12

1. PKC activates

2. Plasma membrane translocation

Question 13

PKC belongs to a family of….

Answer 13

ten serine/threonine kinases that are classified into three subfamilies based on their ligand and cofactor requirements

Question 14

Importance of PKC

Answer 14

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