Downstream of PIP3 Signal Integration Flashcards
1
Q
What domain can be used to image PIP3 production?
A
Akt PH domain
2
Q
What kind of proteins does PIP3 cluster?
A
PH domain containing
3
Q
Give 2 examples of proteins which interact with PIP3
A
- AKT
- PDK1
4
Q
What kind of molecule is AKT?
A
Ser/Thr kinase
5
Q
Give 3 examples of receptors linked to Akt/PI3K
A
- GFR
- Insulin R
- Enzyme linked receptors
6
Q
Outline the role of AKT in insulin signalling in fat cells
A
- 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
7
Q
What are the features of 14.3.3 proteins?
A
- Bind pSer/pThr motifs
- Bind to diverse signalling proteins
8
Q
Outline the role of AKT in insulin signalling in liver cells
A
- AKT phosphorylates FoxO1 to facilitate glucose storage
- Turns off transcription factors which constitutively turn on genes for gluconeogenesis
9
Q
How does AKT regulate cell survival?
A
- Phosphorylates BAD to inhibit apoptosis
- Phosphorylation of BAD is recognised by 14.3.3 proteins which inhibits BAD protein function
10
Q
Why are PTEN mutants so common in cancer?
A
- 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
11
Q
What kind of molecule is GSK3?
A
Serine kinase
12
Q
What is a key target for GSK3?
A
c-myc
13
Q
What is c-myc?
A
A transcription factor
14
Q
What is the role of AKT in c-myc regulation?
A
- When active AKT inactivates GSK3 by phosphorylation
- so c-myc is not degraded and can act as a transcription factor for proliferative signals
15
Q
What is the function of GSK3?
A
- Integrates signals from many places
- Phosphorylates targets which marks them for degradation via ubiquitination
