PIP3 Signalling Revision

Question 1

What dephosphorylates PIP₃ to PIP₂?

Answer 1

PTEN

Question 2

What is the primary substrate for formation of PIP₃?

Answer 2

PIP₂

Question 3

What do class 1A PI3 kinases couple to?

Answer 3

RTKs via SH2 domains will bind to phosphorylated tyrosine residues

Question 4

What is the structure of Class IA PI3 kinases?

Answer 4

• Heterodimers between p85 regulatory subunit and one of 3 catalytic subunits (p110 alpha, beta, or gamma)

Question 5

What bridges the form of a dimer in Class 1A PI3K?

Answer 5

SH2 domains

Question 6

do 1B PI3 kinases have SH2 domains? and are they coupled to RTKs?

Answer 6

They do not have SH2 domains and are not coupled to RTKs

Question 7

What do 1b PI3 kinases bind to?

Answer 7

βγ subunits of heterotrimeric G proteins so the complex is activated downstream of GPCR activation

Question 8

What is a PH domain structure?

Answer 8

7 beta sheets sealed at the top by an alpha helix

Question 9

What does a PH domain do?

Answer 9

Senses PIP₃

Question 10

How does PH domain associate with phosphorylated state of PIP3?

Answer 10

Positive Lys and Arg amino acids are oriented so they interact with PIP3

Question 11

In absence of growth factor stimulation what happens to PIP3 levels and why?

Answer 11

Flux of PI3 kinase activity but PTEN overides this to keep PIP₃ levels low

Question 12

What does PIP3 drive?

Answer 12

Regulated plasma membrane recruitment of proteins containing PIP3 binding PH domains

Question 13

When stimulated with EGF where is PKB found? Why?

Answer 13

• On cytoplasmic leaflet of plasma membrane
• Because EGF receptor dimerises, activates kinases and increases PIP3 concentration
• PKB can bind to PIP3 at leaflet of membrane