Cell growth + division lecture 7

Question 1

PI3K signalling

Answer 1

• Heterodimer, p85 + p110
• p85 = SH2, SH3
• PIP2 → PIP3
• ds effector = Akt/Pkb

Question 2

PKB/Akt

Answer 2

• Ser/Thr kinase
• Use 2 structurally distinct inhibitors of PI3K + blocks PKB activity
• Thr in kinase domain T loop, Ser in CTD
• Mutation of either → Ala
• PDK1 phosph Thr
• PIP3 brings substrate to kinase, allows PDK1 to phosph Pkb
• mTORC2 phosph ser
• To activate PKB, need PI3K, PDK1, mTORC2

Question 3

Localisation

Answer 3

• PKB is activated at plasma membrane, disc + moves e.g. to nucleus

Question 4

PKB substrates

Answer 4

1. Metabolism (GSK3 inhibited → GS activated), PFK2 stimulates glycolysis)
2. Cell cycle control (GSK3 phosph cyclin D, inactivate GSK3 → cyclin D ↑, p21/p27)
3. Cell growth (S6 kinase, CIF-4e, Aka inhibits TSC1/2, Rcb, TORC1, S6K phosph x inhibit 4E-BP)
4. Cell survival/apoptisis (BAD-BclX, phosph to interact w/ 14-3-3, cell survives)

Question 5

Ras

Answer 5

• RTK phosph → assoc of GRB2 → SOS → Ras active → Raf → MEK
• Cross talk
• Myc ↑ expression of cyclin D, SCF subunit, ↑ E2F synthesis