9. Tyrosine kinases

Question 0

what does tyrosine kinase do

Answer 0

role in signal transduction

binds to ligands that eventually induce change in cell be a) altered protein function or b) altered gene expression

Question 1

2 tyrosine kinase families?

Answer 1

1. Receptor Tyrosine Kinases

2. Receptor-Associated Tyrosine Kinases

Question 2

when tyrosine kinase is part of the cell surface receptor, called

Answer 2

receptor protein tyrosine kinase (RPTK)

Question 3

when tyrosine kinase is recruited to the cell surface receptor, called

Answer 3

receptor associated tyrosine kinase

Question 4

examples of RPTKs?

Answer 4

insulin receptor
VEGF
EGF

Question 5

RPTK structure

Answer 5

3 protein domains:

1. globular EC
2. transmembrane
3. tyrosine kinase

Question 6

globular EC domain

Answer 6

responsible for ligand binding

Question 7

transmembrane domain

Answer 7

connects EC domain with the cystolic/tyrosine kinase domain

Question 8

tyrosine kinase domain

Answer 8

CATALYTIC domain

responsible for cellular signaling

Question 9

activation of RPTK

Answer 9

1. ligand binds to 2 RPTKs, causes dimerization of 2 monomeric units
2. dimerization causes activation of the catalytic domain
3. which causes intermolecular transautophosphorylation
4. phosphorylated cytoplasmic domains will then phosphorylate substrates that are recruited to bind to the phosphorylated tyrosine residues

Question 10

tyrosine kinase phosphorylation does NOT ______ but, rather ______

Answer 10

induce conformational change

creates binding sites for proteins that are specific to phosphorylated tyrosine residues

Question 11

all AA sequences that allow binding to recruited substrates need to have?

Answer 11

highly specific AA sequence

phosphotyrosine residue

Question 12

there is a very low concentration of recruited substances within the cell, and the tyrosine kinase has a very LOW AFF for recruited substrates, so how does this reaction even occur?

Answer 12

via SH2 DOMAIN

Question 13

what do SH2 domains do?

Answer 13

localize substrates around the tyrosine kinase domain of the receptor

(so, even if low substrate concentration in cytoplasm, rxn can proceed–counteracts high Km)

Question 14

RATKs

Answer 14

do not have a tyrosine kinase domain attached to them

recruit RAPTKs in order to provide catalytic activity

Question 15

JAK structure

Answer 15

3 domains

1. FERM (responsible for binding to the receptor)
2. kinase (responsible for phosphorylating activity)
3. SH2

Question 16

before JAKs can provide tyrosine kinase activity, then need to?

Answer 16

phosphorylate each other

Question 17

after JAKs phosphorylate each other?

Answer 17

they can phosphorylate the tyrosine residues on the cytoplasmic domain of the receptor itself

then, protein substrates can be recruited to the phosphotryosines

Question 18

what do JAK and Src kinases have in common?

Answer 18

they can affect many different functions inside the cell, from transcription to protein activity

Question 19

what are STATs?

Answer 19

Signal Transducers & Activators of Transcription

recruited proteins that attach to the phosphotyrosine residues on the receptor that were phosphorylated by the JAK/Src

Question 20

do STATs have SH2 domains?

Answer 20

yep

Question 21

why is JAK/STAT signaling important?

Answer 21

because it allows DIRECT signaling access to the nucleus through STAT dimerization

Question 22

2 ways tyrosine kinase signaling can be terminated?

Answer 22

1. via SOCS

2. via PTP

Question 23

what are SOCSs and what do they do?

Answer 23

SOCS: suppressors of cytokine signaling

used as a feedback mechanism in order to prevent continuous activation of RAPTKs

Question 24

SOCS mechanism

Answer 24

JAKs/Srcs activate STATs, causing them to dimerize

STAT dimer travels to the nucleus to begin transcription of several genes
one of these genes codes for the SOCS protein–which can bind to phosphotyrosines from the SH2 domain and prevent any further signaling

Question 25

what are PTPs and what do they do

Answer 25

Protein Tyrosine Phosphatases

they stop tyrosine kinase signal transduction

Question 26

mechanism of PTPs?

Answer 26

1. dephosphorylating the receptor itself

2. dephosphorylating the recrutied subtrates after being activated