PIP2 Membrane Levels + PIP3

Question 1

What does PIP2 concentration act as a rate limiting factor for?

Answer 1

PLC-β and PIP3 activity

Question 2

How is PIP2 resynthesised?

Answer 2

resynthesis of the substrate initiated by phosphatidylinositol-4-kinase (PI4K) after depletion is important for signalling

Question 3

How do [Ca2+]i signals impact PIP2 levels?

Answer 3

hormonal stimulation hydrolyses PIP2

it can also strongly stimulate PIP2 synthesis by acceleration of PI kinases (Loew, 2007)

Question 4

Give an example of a Ca2+ pathway that influences PIP2 levels?

Answer 4

Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1), a signalling molecule with a wide spectrum of actions (Burgoyne & Weiss, 2001

Question 5

How does NCS-1 influence PIP2 levels?

Answer 5

up-regulation of PI4-kinase, the first step in PIP2 synthesis from PI (Zhao et al. 2001)

Question 6

What does PI3K do to PIP2?

Answer 6

3′ phosphorylation

Question 7

What does 3′ phosphorylation of PIP2 do?

Answer 7

proteins containing PH and PH-like domains are recruited to the plasma membrane, thereby transmitting the signal elicited by PI3K activation (Engelman et al., 2006)

Question 8

What does PIP3 recruitment of PH containing proteins do?

Answer 8

Association with PIP3 at the membrane brings these proteins into proximity and facilitates phosphorylation of Akt by the phosphoinositide-binding protein, PDK1 (Alessi et al.,1997) and the protein complex, mTORC2 (Sarbassov et al.,2004;2005)

Question 9

What does Akt phosphorylation do?

Answer 9

This phosphorylation stimulates the catalytic activity of Akt, resulting in the phosphorylation of a host of other proteins that affect cell growth, cell cycle entry, and cell survival

Question 10

What does activated Akt do?

Answer 10

Most of the known protein targets of Akt become inhibited by the phosphorylation event.

Question 11

What is an example of Akt activity?

Answer 11

phosphorylation of the Forkhead-related transcription factor 1 (FKHR-L1) by Akt creates a binding site for the 14-3-3 family of proteins (Brunet et al.,2001)

Question 12

How does phosphorylation of FKHR-L1 lead to inhibition?

Answer 12

The complex of FKHR-L1 and 14-3-3 is retained in the cytosol, blocking transcription of genes normally stimulated by FKHR-L1

Question 13

Up to how many substances does Akt phosphorylate?

Answer 13

AKT phosphorylates up to 100 substrates

Question 14

What are the implications of Akt phosphorylation events?

Answer 14

PI3K-AKT axis is considered the canonical PI3K signaling