Downstream of PIP3 Signal Integration

Question 1

What domain can be used to image PIP3 production?

Answer 1

Akt PH domain

Question 2

What kind of proteins does PIP3 cluster?

Answer 2

PH domain containing

Question 3

Give 2 examples of proteins which interact with PIP3

Answer 3

• AKT
• PDK1

Question 4

What kind of molecule is AKT?

Answer 4

Ser/Thr kinase

Question 5

Give 3 examples of receptors linked to Akt/PI3K

Answer 5

• GFR
• Insulin R
• Enzyme linked receptors

Question 6

Outline the role of AKT in insulin signalling in fat cells

Answer 6

• 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

Question 7

What are the features of 14.3.3 proteins?

Answer 7

• Bind pSer/pThr motifs
• Bind to diverse signalling proteins

Question 8

Outline the role of AKT in insulin signalling in liver cells

Answer 8

• AKT phosphorylates FoxO1 to facilitate glucose storage
• Turns off transcription factors which constitutively turn on genes for gluconeogenesis

Question 9

How does AKT regulate cell survival?

Answer 9

• Phosphorylates BAD to inhibit apoptosis
• Phosphorylation of BAD is recognised by 14.3.3 proteins which inhibits BAD protein function

Question 10

Why are PTEN mutants so common in cancer?

Answer 10

• 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

Question 11

What kind of molecule is GSK3?

Answer 11

Serine kinase

Question 12

What is a key target for GSK3?

Answer 12

c-myc

Question 13

What is c-myc?

Answer 13

A transcription factor

Question 14

What is the role of AKT in c-myc regulation?

Answer 14

• When active AKT inactivates GSK3 by phosphorylation
• so c-myc is not degraded and can act as a transcription factor for proliferative signals

Question 15

What is the function of GSK3?

Answer 15

• Integrates signals from many places
• Phosphorylates targets which marks them for degradation via ubiquitination

Question 16

Without AKT what is does GSK3 do to c-myc?

Answer 16

• Phosphorylates c-myc and labels it for degradation via ubiquitination

Question 17

What kinase does mTORC1 contain?

Answer 17

mTOR kinase

Question 18

What is the role of mTORC1 once activated by AKT?

Answer 18

• mTORC1 phosphorylates and activates S6 kinase
• which phosphoryles rS6 ribosomal subunit which activates ribosome activity

Question 19

What does mTORC1 act as a sensor for?

Answer 19

Nutrients

Question 20

What activates mTORC1?

Answer 20

AKT

Question 21

How does mTORC1 affect mRNA translation?

Answer 21

• Regulates 4E-BP1 binding protein which binds to mRNA to prevent mRNA translation
• mTORC1 prevents this binding and cell growth occurs