Cell Cycle 7

Question 1

What is the viral mutant of EGFR called?

Answer 1

v-ErB2

Question 2

What is altered in the viral mutant of Akt?

Answer 2

It is constitutively bound at the plasma membrane.

Question 3

What growth factor was identified in the media of cancer cells?

Answer 3

TGFB

Question 4

What antibody blocked the binding of TGFB?

Answer 4

c225

Question 5

What did Cohen discover and how?

Answer 5

EGF - injected new born mouse saliva into eyes and found that they opened earlier.

Question 6

How many disulphide bonds are there in EGF?

Answer 6

3

Question 7

What does EGF bind?

Answer 7

EGFR

Question 8

When EGF binds EGFR, what happens to the receptor?

Answer 8

It dimerises and undergoes trans-auto-phosphorylation.

Question 9

Which two proteins bind to phosphorylated tyrosines on EGFR?

Answer 9

Grb2 and PI3K via SH2 domains

Question 10

What binding domains does Grb2 have?

Answer 10

One SH2 domain and two SH3 domains either side

Question 11

What does Grb2 bind via its SH3 domains?

Answer 11

Binds two proline rich sequences in Sos

Question 12

What is the function of Sos when at PM?

Answer 12

It catalyses the nucleotide exchange for Ras protein.

Question 13

What groups allow Ras to attached to the PM?

Answer 13

Farnesyl groups

Question 14

What pathway is downstream of activated Ras?

Answer 14

MAP kinase pathway

Question 15

How does Ras activate Raf?

Answer 15

Allosterically

Question 16

What does Raf phosphorylate? and what does this cause?

Answer 16

Mek, which in turns phosphorylates Erk

Question 17

What does Erk do?

Answer 17

Phosphorylates the TFs jun and fos - these activate the expression of cyclin D.

Question 18

What does PI3K phosphorylate?

Answer 18

The inositol head group of lipids, on position 3 - to give PIP3

Question 19

What is recruited by PIP3 and via what domain?

Answer 19

PDK1 and Akt - have PH domains which bind to PIP3.

Question 20

What is a PH domain made up of?

Answer 20

Many beta strands and one alpha helix - the loop between provides specificity.

Question 21

What type of kinases are PDK1 and Akt?

Answer 21

Serine/Threonine kinases

Question 22

Is PDK1 constitutively active?

Answer 22

Yes

Question 23

What does recruiting of PDK1 and Akt to PM allow?

Answer 23

Allows for phosphorylation on T308 of Akt by PDK1, activating it.

Question 24

What are the 4 downstream effects of Akt?

Answer 24

1. Phosphorylates GSK3 on Ser9, this prevents inhibition of cyclins.
2. Phosphorylation of FOXO (TF), causing nuclear export and preventing expression of p27.
3. Phosphorylation of p27 - nuclear export
4. Phosphorylation of p21, causing degradation.

Question 25

What does PTEN do?

Answer 25

It is a phosphatase that removes phosphorylation from inositol head groups. This prevents Akt and PDK1 binding.

Question 26

Is PTEN a tumour supressor?

Answer 26

Yes

Question 27

Give the name of the drug that prevents farnesylation of Ras.

Answer 27

Farnesyltransferase inhibitors - prevent membrane localisation of Ras.

Question 28

What drug targets the V600E mutation in constitutively Raf?

Answer 28

PLX4032