enzyme-coupled receptors

Question 1

what does RTK stand for

Answer 1

receptor tyrosine kinase

Question 2

what is a receptor tyrosine kinase an example of

Answer 2

an enzyme-coupled receptor

Question 3

what type of enzymatic activity does a receptor tyrosine kinase have

Answer 3

intrinsic

Question 4

where in the cell are RTKs located

Answer 4

membranes

Question 5

what are the two domains of an RTK

Answer 5

cytosolic and extracellular

Question 6

where does a ligand bind to an RTK

Answer 6

extracellular domain

Question 7

describe the structure of the RTK that spans the membrane

Answer 7

transmembrane alpha helix

Question 8

describe the cytosolic domain of an RTK

Answer 8

it contains protein tyrosine kinase activity

Question 9

list some possible ligands for an RTK

Answer 9

growth factors (NGF, FGF, EGF), insulin

Question 10

T or F: most RTKs are monomeric

Answer 10

true

Question 11

how is the intrinsic kinase activity of an RTK activated

Answer 11

binding of a ligand = dimerization = activation of kinase activity

Question 12

what happens once RTKs dimerize

Answer 12

trans-autophosphorylation (each monomer phosphorylates the other)

Question 13

what does trans-autophosphorylation do

Answer 13

activates kinase domains

Question 14

what happens after trans-autophosphorylation

Answer 14

conformational change that fully activates kinase activity, then autophosphorylation

Question 15

what happens to the RTK after autophosphorylation

Answer 15

it generates binding sites for signaling proteins which can now become activation, and now can relay the signal downstream

Question 16

what pathway do RTKs activate

Answer 16

Ras/MAP pathway

Question 17

what is Ras

Answer 17

a monomeric G protein

Question 18

what is Ras activated by

Answer 18

GEF

Question 19

where is Ras within the cell

Answer 19

anchored to the cytoplasmic side of the PM by a covalently attached lipid

Question 20

T or F: Ras interacts directly with the RTK

Answer 20

false! there is no direct interaction

Question 21

what two proteins serve as linkers between Ras and RTK

Answer 21

GRB2 and Sos

Question 22

describe the process of indirect activation of Ras by RTK

Answer 22

Ras=GDP bound (inactive). GRB2 interacts with active RTK via it’s SH2 domain and with SoS via it’s SH3 domain. This brings Sos to the PM to interact with Ras. Sos=GEF=Ras is GTP bound (active). Ras can now activate a downstream effector (its target)

Question 23

what 3 proteins are involved in the MAP kinase module

Answer 23

Raf, MEK, Erk

Question 24

describe how Ras activates the MAP kinase module

Answer 24

Ras activates Raf via direct contact. Raf activates Mek via phosphorylation, Mek activates Erk via phosphorylation. Erk can now phosphorylate different things

Question 25

what is one turn off mechanism of the MAP kinase module

Answer 25

phosphorylation of Raf by Erk

Question 26

what does the c-fos gene encode for

Answer 26

proteins that help cells progress through the cell cycle

Question 27

T or F: most RTKs that bind GFs will initiate the transcription of genes that encode for proteins that help cells progress through the cell cycle

Answer 27

true

Question 28

what is the c-fos gene regulated by

Answer 28

an enhancer (SRE)

Question 29

what does SRE stand for

Answer 29

serum response element

Question 30

what is SRE an enhancer for

Answer 30

transcription of the c-fos gene

Question 31

describe the pathway of c-fos transcription enhancement

Answer 31

Erk phosphorylates p90RSK (a kinase) to activate it, then it moves into the nucleus and phosphorylated SRF (serum response factor, a TF). Two phosphorylated SRFs bind to SRE

meanwhile. MAP kinase moves into the nucleus and phosphorylated TCF (ternary complex factor) which is bound to SRE. The trimeric complex on SRE stimulates transcription of c-fos

Question 32

what is the role of scaffolding proteins

Answer 32

they help to keep the kinases involved in a particular pathway interacting ONLY with each other (prevents cross-talk between pathways)

Question 33

define convergence

Answer 33

2 pathways intersect at certain points

Question 34

define cross-talk

Answer 34

signals within the same pathway affecting other signals in that pathway