Downstream of PIP3 Signal Integration Flashcards
What domain can be used to image PIP3 production?
Akt PH domain
What kind of proteins does PIP3 cluster?
PH domain containing
Give 2 examples of proteins which interact with PIP3
- AKT
- PDK1
What kind of molecule is AKT?
Ser/Thr kinase
Give 3 examples of receptors linked to Akt/PI3K
- GFR
- Insulin R
- Enzyme linked receptors
Outline the role of AKT in insulin signalling in fat cells
- Insulin binds to receptor and causes phosphorylation of receptor tail
- Activation of PI3K recruits and activates AKT
- As160 phosphorylated and 14.3.3 binds and inactivates As160 increases RabGTP and Glut4 opens
What are the features of 14.3.3 proteins?
- Bind pSer/pThr motifs
- Bind to diverse signalling proteins
Outline the role of AKT in insulin signalling in liver cells
- AKT phosphorylates FoxO1 to facilitate glucose storage
- Turns off transcription factors which constitutively turn on genes for gluconeogenesis
How does AKT regulate cell survival?
- Phosphorylates BAD to inhibit apoptosis
- Phosphorylation of BAD is recognised by 14.3.3 proteins which inhibits BAD protein function
Why are PTEN mutants so common in cancer?
- PTEN activity has a role in reducing survival signals
- When missing cell is in anti-apoptotic state
- Without PTEN cells don’t apoptose in response to DNA damage
What kind of molecule is GSK3?
Serine kinase
What is a key target for GSK3?
c-myc
What is c-myc?
A transcription factor
What is the role of AKT in c-myc regulation?
- When active AKT inactivates GSK3 by phosphorylation
- so c-myc is not degraded and can act as a transcription factor for proliferative signals
What is the function of GSK3?
- Integrates signals from many places
- Phosphorylates targets which marks them for degradation via ubiquitination
Without AKT what is does GSK3 do to c-myc?
- Phosphorylates c-myc and labels it for degradation via ubiquitination
What kinase does mTORC1 contain?
mTOR kinase
What is the role of mTORC1 once activated by AKT?
- mTORC1 phosphorylates and activates S6 kinase
- which phosphoryles rS6 ribosomal subunit which activates ribosome activity
What does mTORC1 act as a sensor for?
Nutrients
What activates mTORC1?
AKT
How does mTORC1 affect mRNA translation?
- Regulates 4E-BP1 binding protein which binds to mRNA to prevent mRNA translation
- mTORC1 prevents this binding and cell growth occurs
