11. Receptor Tyrosine Kinases

Question 1

give two examples of receptor tyrosine kinases

Answer 1

platelet derived growth factor receptor

insulin receptor

Question 2

what are platelet derived growth factor receptors involved in

Answer 2

embryonic development

cell proliferation & migration

Question 3

on epidermal growth factor receptors, what is the ligand

Answer 3

epidermal growth factor

Question 4

what is epidermal growth factor involved in

Answer 4

cell growth
proliferation
differentiation

Question 5

what does the cytosolic domain of a RTK contain

Answer 5

a c-terminal tyrosine rich tail

Question 6

what happens when the ligand binds

Answer 6

binding of the ligand creates a conformational change

which exposes the dimerisation arm

dimerisation arms interact and dimerisation occurs

Question 7

which region of the RTK contains the dimerisation arm, when is It available

Answer 7

region 2

- only visible when the receptor is stimulated

Question 8

what does dimerisation induce

Answer 8

autophosphorylation on tyrosine residues on the activation lip of tyrosine kinase

Question 9

what are the phosphorylated residues often used as?

Answer 9

docking sites between proteins to allow interactions and for the signal to be transducer from the receptor down through the signalling cascade

Question 10

how do kinases interact

Answer 10

asymmetrically

Question 11

explain the roles of acceptor and donor kinases

Answer 11

acceptor kinase is activated by donor kinase which moves out from the active site

= phosphorylation

Question 12

what does MAPK stand for

Answer 12

mitogen activated protein kinease

Question 13

what is GRB

Answer 13

an adaptor protein

Question 14

what domains does GRB contain

Answer 14

SH2 and SH3

Question 15

what does the SH2 domain in GRB interact with

Answer 15

phospho-tyrosine residues

Question 16

what can GRB2 do that GRB cannot

Answer 16

bind to phospho-tyrosine residues on other proteins

Question 17

what can GRB2’s SH3 domain bind

Answer 17

Sos

Question 18

how does GRB2 bind to RTKs

Answer 18

via its SH2 domain

Question 19

what does SOS bind to

Answer 19

Ras

Question 20

what must be activated to recruit downstream signalling proteins

Answer 20

monomeric G-protein Ras

Question 21

what allows Ras to bind GTP or GDP

Answer 21

a guanyl nucleotide binding site

Question 22

what enzyme converts GTP into GDP as soon as GTP binds

Answer 22

intrinsic GTPase activity

Question 23

what molecule promotes GDP exchange for GTP

Answer 23

guanine nucleotide- exchange factor (GEF)

Question 24

what molecule accelerates GTP hydrolysis

Answer 24

GTPase-activating protein

Question 25

what is the function of Sos

Answer 25

pries Ras open - allowing GDP to diffuse out - promoting GTP binding

Question 26

what displaces Sos

Answer 26

switch I & II interacting with GTP

Question 27

what happens when Sos dissociates from Ras

Answer 27

Ras is then free to activate downstream signalling components

Question 28

what is responsible for 50% of colorectal tumours

Answer 28

a single activating point mutation in the K-ras oncogene - interferes with GTPase activity

Question 29

now that Ras is activated, what does it next bind to

Answer 29

the N-terminal of Raf

Question 30

what activates Raf

Answer 30

dephosphorylation of a serine that binds Raf to regulatory proteins

Question 31

what causes Raf to dissociate from the 14-3-3 regulatory protein

Answer 31

hydrolysis of GTP = Ras-GDP

Question 32

what does Raf kinase phosphorylate

Answer 32

MEK

Question 33

what is the name of the regulatory protein Raf is bound to

Answer 33

14-3-3

Question 34

once activated, what does MEK next activate>

Answer 34

another kinase called MAPK

Question 35

what is MAPK called in humans

Answer 35

ERK

Question 36

what does MEK use to activate the MAPK

Answer 36

MAP kinase kinase

Question 37

what is Raf

Answer 37

a MAP kinase kinase kinase

Question 38

what does active MAPK do

Answer 38

dimerises and phosphorylates protein kinase | p90

Question 39

where do active MAPK and p90 migrate to

Answer 39

the nucleus

Question 40

what does MAPK and p90 do in the nucleus

Answer 40

phosphorylates TCF and SRF

Question 41

what does TCF stand for

Answer 41

ternary complex factor

Question 42

what does SRF stand fro

Answer 42

serum response factor

Question 43

what does phosphorylated SRF and TCF bind to?

Answer 43

serum response element | SRE