Lecture 9

Question 1

what is transautophosphorylation in RTKs

Answer 1

phosphorylate each other in the dimerized state that generates binding sites for signaling molecules
like a scaffold protein

Question 2

what domains can signaling molecules bind to RTKs

Answer 2

SH2 and PTB

Question 3

where does specificity come from for SH2 domains?

Answer 3

1. recognizes phosphorylated tyrosine
2. recognizes nearby amino acid

overall because of 2 binding domains in the signal protein - one for amino acid, one for phosphotyrosine

Question 4

what does Ras GEF do

Answer 4

exchange GDP for GTP on Ras small monomeric G protein
GTP bound Ras is active

Question 4

why do many cancers have overactive Ras

Answer 4

promoting cell survival when cancer cells should not survive

Question 5

what does GTP bound Ras activate?

Answer 5

activates MAP kinase cascade - series of kinases that pass on signals
1. MAP kinase kinase kinase (raf)
2. MAP kinase kinase (mek)
3. MAP kinase (erk)
4. other targets

Question 6

MAP

Answer 6

mitogen-activated protein kinase

Question 7

does Ras activate MAP kinase kinase kinase by phosphorylation

Answer 7

no! some other way

Question 8

sevenless signaling

Answer 8

RTK = sevenless (sev)
ligand = Boss (bride of sevenless)
adaptor protein = Grc

Question 9

what is Boss

Answer 9

protein expressed in plasma membrane of R8 cell
ligand of sevenless receptor in R7 cells
contact dependant signaling

Question 10

what does the first transautophosphorylation do in sevenless signaling

Answer 10

makes kinase more active to phosphorylate other tyrisine residues in the receptor

Question 11

what is son of sevenless?

Answer 11

Sos is Ras-GEF to activate nearby Ras by exchanging GTP for GDP which can then go activate a MAP kinase cascade to activate differential genome expression by phosphorylating transciptional regulators

Question 12

what is the protein connecting Sos and sevenless?

Answer 12

Grb2 (Drk) is the adapter protein that binds to the activated receptor on Sev

Question 13

does sevenless signal for cell division or cell differentiation

Answer 13

differentiation: end result targes transcriptional regulators

Question 14

RTK and PIPs

Answer 14

RTK signals PI3 kinase
kinase phosphorylates PIP
serine/threonine kinase proteins PDK and Akt with PH domains then bind to PIP
active AKT releases and phosphorylates Bad releasing Bcl to inhibit apoptosis

Question 15

do all receptor proteins have a kinase domain

Answer 15

no

Question 16

are serine/threonine kinases similar to RTKs

Answer 16

yes, just phosphorylate serine/threonine domains