L16 - PIP3 and the elixir of life

Question 1

what is Akt otherwise known as and what is it

Answer 1

Protein Kinase B

= serine/threonine kinase

Question 2

describve the steps involed in activation of Akt

Answer 2

1. binding of growth factors/ligands to RTKs
2. RTKs activate P13K

= PIP2 –> PIP3 at membrane

3. Akt recruited to membrane via PH domain + binbds PIP3
4. 2 key kinases then phosphoykare Akt:
   - PDK1 -> threoinine
   - mTORC2 -> serine

= fully actiavtes Akt allowing it to phosphory;ate dfownstream targets

Question 3

name the 2 kinases that phosphorylate AKt/Protein Kinase B when recruited to PIP3 at membrane

Answer 3

PDK1 = Threonine residues

mTORC2 = Serine residues

Question 4

how does Akt affect glucose metabolism

Answer 4

AKt actiavte GLUT4 translocation to membrane

• increase in glucose uptake in cells

Question 5

how does Akt affect survival/anti-apoptic signals

Answer 5

inhibits caspase-9 activity

Question 6

how does Akt affect cell growth and proliferation

Answer 6

Akt activates mTORC1 –> master regulator of protein synethsis

(different to mTORC2 which activates Akt)

Question 7

what is mTOR

Answer 7

mechanistic target of rapmycin - serine/threonine kinase

exists in 2 complexes:
- mTORC1 = master regulator of protein synthesis
- mTORC2 = Akt activation

Question 8

what is rapamycin

Answer 8

mTORC inhibitor - the master regulator of protein synthesis

binds to FKBP12 = complex that inhibits mTORC1

= decrease protein synthesis
= can be used as an immunosuppressant or cancer therapy