Insulin Signalling

Question 1

How does TSC2 affect protein synthesis?

Answer 1

TSC2 is GAP converting Rheb-GTP to Rheb-GDP
Rheb-GTP activates mTORC1
Ins signalling –> TSC2 no longer binds TSC1 and loses GAP activity
can’t hydrolyse Rheb-GTP
CONTINUED MTORCI activation and protein synthesis.

Question 2

what is the role of PDK1?

Answer 2

activates Akt once it is at the membrane.

There are three types in humans encoded by different genes.

Question 3

What are the main targets of akt?

Answer 3

Anti-apoptotics e.g. Mdm2 (negative regulator of p53 tumour suppressor, E3 ligase and inhibitor of transcriptional activation).

Inhibits apoptotic e.g. Bad / p21 / Tsc2.

Question 4

Describe TSC1 and 2.

Answer 4

TSC1 encodes hamartin which interacts with tuberin from TSC2.
RSC2 phosphorylated by Akt.
The unphosphorylated form inhibits Rheb which then activates mTOR.

Question 5

What is the effect of FOXO overexpression?

Answer 5

inhibition of transcription and a longer lifespan in FLIES!