L15 - P13 Kinases

Question 1

how do P13K and PTEN work in regulation of PIP3 at plasma membranes

Answer 1

P13K -> adds phosphate to phosphoinositides -> PIP3 formed

PTEN -> removes the phosphate

Question 2

describe activation and then inactivation of PIP3 by P13K and PTEN

Answer 2

1. P13 actiavted downstream of RTKs
2. P13K phosphorylates PIP2 at 3’ position –> PIP3

= PIP3 on inner leaflet of membrane acts as docking site for signalling proteins in growth and survival

3. PTEN reoves phosphate PIP3 –> PIP2

= signal stopped

Question 3

what does overproduction of PIP3 cause

Answer 3

abnormal cell proliferation and survival –> cancer

= Akt pathway

Question 4

describe how PIP3 is relavenat in cancer giving examples of P13K and PTEN

Answer 4

overproduction of PIP3

–> P13K hyperactivation

PTEN is a TSG = fremoves phosphate fro PIP3

without PTEN:
- PIP3 build up
- Akt hyperactivation

= uncontrolled cell growth

Question 5

what are PH domains

Answer 5

Pleckstrin homology domains

= protein domains that bind to phosphoinositides
= PIP3

Question 6

how do PH domains decetct PIP3

Answer 6

1. proteins like AKT and PDK1 have PH domains
2. PIP3 generation at membrabne

= PH domains bind and recruit proteins to membrane
= Akt phosphoylated and activated by PKK1 and mTORC