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211: Cell Biology > 11. Receptor Tyrosine Kinases > Flashcards

11. Receptor Tyrosine Kinases Flashcards

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1
Q

give two examples of receptor tyrosine kinases

A

platelet derived growth factor receptor

insulin receptor

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2
Q

what are platelet derived growth factor receptors involved in

A

embryonic development

cell proliferation & migration

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3
Q

on epidermal growth factor receptors, what is the ligand

A

epidermal growth factor

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4
Q

what is epidermal growth factor involved in

A

cell growth
proliferation
differentiation

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5
Q

what does the cytosolic domain of a RTK contain

A

a c-terminal tyrosine rich tail

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6
Q

what happens when the ligand binds

A

binding of the ligand creates a conformational change

which exposes the dimerisation arm

dimerisation arms interact and dimerisation occurs

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7
Q

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

A

region 2

- only visible when the receptor is stimulated

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8
Q

what does dimerisation induce

A

autophosphorylation on tyrosine residues on the activation lip of tyrosine kinase

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9
Q

what are the phosphorylated residues often used as?

A

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

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10
Q

how do kinases interact

A

asymmetrically

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11
Q

explain the roles of acceptor and donor kinases

A

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

= phosphorylation

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12
Q

what does MAPK stand for

A

mitogen activated protein kinease

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13
Q

what is GRB

A

an adaptor protein

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14
Q

what domains does GRB contain

A

SH2 and SH3

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15
Q

what does the SH2 domain in GRB interact with

A

phospho-tyrosine residues

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16
Q

what can GRB2 do that GRB cannot

A

bind to phospho-tyrosine residues on other proteins

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17
Q

what can GRB2’s SH3 domain bind

A

Sos

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18
Q

how does GRB2 bind to RTKs

A

via its SH2 domain

19
Q

what does SOS bind to

A

Ras

20
Q

what must be activated to recruit downstream signalling proteins

A

monomeric G-protein Ras

21
Q

what allows Ras to bind GTP or GDP

A

a guanyl nucleotide binding site

22
Q

what enzyme converts GTP into GDP as soon as GTP binds

A

intrinsic GTPase activity

23
Q

what molecule promotes GDP exchange for GTP

A

guanine nucleotide- exchange factor (GEF)

24
Q

what molecule accelerates GTP hydrolysis

A

GTPase-activating protein

25
Q

what is the function of Sos

A

pries Ras open - allowing GDP to diffuse out

  • promoting GTP binding
26
Q

what displaces Sos

A

switch I & II interacting with GTP

27
Q

what happens when Sos dissociates from Ras

A

Ras is then free to activate downstream signalling components

28
Q

what is responsible for 50% of colorectal tumours

A

a single activating point mutation in the K-ras oncogene

  • interferes with GTPase activity
29
Q

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

A

the N-terminal of Raf

30
Q

what activates Raf

A

dephosphorylation of a serine that binds Raf to regulatory proteins

31
Q

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

A

hydrolysis of GTP

= Ras-GDP

32
Q

what does Raf kinase phosphorylate

A

MEK

33
Q

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

A

14-3-3

34
Q

once activated, what does MEK next activate>

A

another kinase called MAPK

35
Q

what is MAPK called in humans

A

ERK

36
Q

what does MEK use to activate the MAPK

A

MAP kinase kinase

37
Q

what is Raf

A

a MAP kinase kinase kinase

38
Q

what does active MAPK do

A

dimerises and phosphorylates protein kinase

p90

39
Q

where do active MAPK and p90 migrate to

A

the nucleus

40
Q

what does MAPK and p90 do in the nucleus

A

phosphorylates TCF and SRF

41
Q

what does TCF stand for

A

ternary complex factor

42
Q

what does SRF stand fro

A

serum response factor

43
Q

what does phosphorylated SRF and TCF bind to?

A

serum response element

SRE

211: Cell Biology (20 decks)

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