Lecture 13 & 14 (serine/threonine kinases)

Question 1

> 50% of carcinomas overexpress __

Answer 1

EGFR

Question 2

30% of breast cancers overexpress __

Answer 2

HER2

Question 3

~90% of pancreatic cancers have a __ mutation

Answer 3

K-Ras

Question 4

66% of melanoma have a __ mutation

Answer 4

B-RAF (mainly at codon 600 → constitutive activation of MAPK pathway)

Question 5

Best example of serine/threonine kinases

Answer 5

Raf proteins

Question 6

Most cellular kinase activity is on __ residues

Answer 6

serine and threonine

Question 7

3 major branches of Raf family

Answer 7

C-Raf1
A-Raf1
B-Raf1

Question 8

What converts c-Raf proteins to oncogenes?

Answer 8

Deletion of N-terminal regulatory sequences

Question 9

Truncated Raf proteins in retroviruses are expressed as…

Answer 9

fusion proteins (Gag/Raf or cellular gene/Raf product)

Question 10

Examples of serine/threonine kinases

Answer 10

• Protein kinase C family
• Mos
• Pim-1

Question 11

PKC is an intracellular target for activation by…

Answer 11

tumour-promoting phorbol esters (mimic the activity of DAG)

Question 12

Catalytic activity of PKC requires binding of __ and __

Answer 12

Ca²⁺ and phospholipid

Question 13

Limited proteolysis __ PKC

Answer 13

activates

Question 14

Strong analogy between PKC activation by cleavage and…

Answer 14

Raf activation by N-terminal deletion

Question 15

Overexpression of PKC can induce…

Answer 15

cell transformation

Question 16

What cells mainly express mos?

Answer 16

germ cells

Question 17

Does mos have an N-terminal regulatory sequence?

Answer 17

No

Question 18

How was the Pim-1 oncogene identified?

Answer 18

by retroviral insertional mutagenesis in mouse T lymphomas

Question 19

Another name for Raf

Answer 19

MAP-KKK

Question 20

Ras interacts with __ , which leads to the formation of filopodia and lamellipodia

Answer 20

Ral-GEF protein

Question 21

What does PIP3 activate?

Answer 21

Akt (PKB) + Rho proteins

Question 22

The 2 major types of drugs that have been developed to treat cancer

Answer 22

Small molecule kinase inhibitors and monoclonal antibodies that will interact with a tyrosine kinase

Question 23

EGFR inhibitor that is used to treat NSCLC

Answer 23

Afatinib

Question 24

Ras is not a serine/threonine kinase itself but leads to the activation of a very important serine/threonine kinase called __

Answer 24

PKB (Akt)

Question 25

PI3K does not phosphorylate proteins, it phosphorylates __

Answer 25

phosphoinositides

Question 26

PIP3 is a binding site for __

Answer 26

Akt

Question 27

What part of PI3K does activated Ras bind?

Answer 27

the p110 catalytic subunit

Question 28

Activated PI3K phosphorylates PIP2 at position __ of the inositol ring

Answer 28

3

Question 29

What is PI3K (heterodimer) comprised of?

Answer 29

a catalytic subunit (p110) and a regulatory subunit (p85)

Question 30

Activated Akt has a number of different targets that it will phosphorylate at serine/threonine residues

Answer 30

- activates cyclin-1 and Raptor - inhibits GSK-3 and Forkhead

Question 31

Phosphatase for PI3K

Answer 31

p10 (converts PIP3 back into PIP2)

Question 32

How can the Akt pathway be activated?

Answer 32

- by binding of P-Tyr residues on RTKs - by activated Ras

Question 33

PI3K pathway regulates various cellular processes such as...

Answer 33

- proliferation - growth - apoptosis - cytoskeletal rearrangement

Question 34

Akt activation involves the phosphorylation of which two residues

Answer 34

Thr308 (by PDK1) and Ser473 (by PDK2)