tyrosine kinase receptors

Question 1

what is a kinase?

Answer 1

an enzyme that catalyses the transfer of a phosphate group from ATP to another molecule

Question 2

what is a receptor tyrosine kinase?

Answer 2

mediate cell-to-cell communication and controlling a wide range of complex biological functions, including cell growth, motility, differentiation, and metabolism

Question 3

two types of RTK

Answer 3

1. ligand binding to a receptor activates kinase domain of the receptor
2. ligand binding to receptor causes change in protein domain and kinase binds to receptor

Question 4

receptor tyrosine kinases vs receptor associated tyrosine kinases

Answer 4

receptor tyrosine kinase is a domain of the ligand receptor
e.g. (insulin/EGF)
receptor associated tyrosine kinase binds to a receptor upon ligand binding
e.g. (Janus Kinase)

Question 5

structure of RTK

Answer 5

1. extracellular domain = ligand binding site
2. transmembrane domain = only one, 1 alpha helix
3. intracellular domain = some have kinase domain
4. Docking sites = cytosolic tail with tyrosine docking sites

Question 6

activation of EGF receptor

Answer 6

1. EGF binds to extracellular domain
2. dimerization occurs: two receptors bind together
3. tyrosine docking sites are phosphorylated
4. phosphorylated Tyr cause relay proteins to bind and activate which amplify cell response

Question 7

EGF

Answer 7

epidermal growth factor

Question 8

what deactivates RTKs

Answer 8

tyrosine phosphatases or degradation

Question 9

key cellular functions of RTK

Answer 9

• growth
• proliferation
• movement
• survival
• differentiation

Question 10

speed of RTK response

Answer 10

slow/hours

Question 11

2 examples of effector functions of RTKs

Answer 11

Ras and PI3-kinase

Question 12

Ras

Answer 12

g-protein that is a target for RTKs.
is a critical relay in signal transduction

Question 13

Ras inactive state

Answer 13

when bound to GDP

Question 14

Ras activated state

Answer 14

when bound to GTP

Question 15

How is Ras activated?

Answer 15

• signal molecule/ligand binds to RTK
• tyrosine docking sights are phosphorylated
• adaptor protein attaches to phosphorylated Tyr
• Ras-activating protein attaches to adaptor protein
• this protein exchanges GDP for GTP in Ras, which activates it
• onward transmission of signal as Ras binds to effectors

Question 16

what activates Ras

Answer 16

GEFs exchange GDP for GTP which activates it

Question 17

what deactivates Ras?

Answer 17

GAPs exchange GTP for GDP which deactivates Ras.
they catalyse GDPs dissociation from Ras

Question 18

GEFs?

Answer 18

guanine nucleotide exchange factors

Question 19

GAPs?

Answer 19

GTPase activating/accelerating proteins

Question 20

simple downstream signalling cascade of Ras (MAPK pathway)

Answer 20

Activate Ras -> activated MAP kinase kinase kinase (RAF)
MAP KKK -> activated MAP kinase kinase (MEK)
MAP KK -> activated MAP kinase (ERK)
finally proteins/transcription regulators are activated
Ras -> RAF -> MEK -> ERK

Question 21

RAF

Answer 21

MAP kinase kinase kinase

Question 22

MEK

Answer 22

MAP kinase kinase

Question 23

ERK

Answer 23

MAP kinase

Question 24

basic PI3K pathways

Answer 24

• ligand bound to RTK
• PI3K binds to phosphorylated Tyr and is activated
• PI3K phosphorylates inositol phospholipid
• the phosphorylated inositol phospholipid is the 2nd messenger
• PIP acts as a docking site for protein kinase 1 which (along with protein kinase 2) activates AKT
• PIP3 also acts as a docking molecule for AKT