Cell signalling and Ageing Flashcards
What happens when you put a mouse in a cage and put it on dietary restrictions?
Extends its lifestyle.
What is an age-1 mutation?
Worms live 2 times longer.
What is a DAF-2 mutation?
Worms live 6.4 times longer.
What is a DAF-16 mutation?
Suppress the increase in positivity of DAF-2 and age-1.
What is DAF-2?
It encodes the insulin receptor.
What is age-1?
A catalytic subunit of pi-3-kinase.
What is DAF-16?
A transcriptional factor of forkhead family.
What are the stages of activation of PI3-kinase by the
insulin receptor.
1 - binding of the ligand
2 - conformational change
3 - trans-phosphorylation
4 - IRS-1 binds phosphotyrosine
5 - IRS-1 is phosphorylated
6 - binding of p85 regulatory subunit of pi3-kinase
What are the stages of activation of protein kinase Akt?
1 - PI3-kinase produces PI products
2 - AKT and PDK1 interact with PI products
* 3 - AKT is phosphorylated
* 4 - Binding to PDK1
* 5 - PDK1 phosphorylates AKT
* 6 - Dephosphorylation of PI-products by PTEN
What is the function of Akt?
Regulates transcription through FOXO.
How does Akt regulate transcription?
- AKT phosphorylates FOXO
- FOXO is excluded from the nucleus and degraded
- Inactivation of genes involved in longevity
What are the 3 main signals that mTORC1 integrates?
- Levels of free amino acids
- IIS signalling
- Energy levels
Draw the small GTPase cycle.
What are the stages of mTORC1 regulation by AKT?
- IIS signalling activates AKT
- AKT phosphorylates TSC2
- Activation of GTPase Rheb
- GTP-bound Rheb activates mTORC1
What are the stages of activation of mTORC1 via the localisation to lysosomal membranes?
- Amino acids recruit mTORC1 to the lysosomal surface
- Amino acids signal the Rag GTPases
- Active Rag GTPases recruit mTORC1 Rheb activates mTORC1
