L9

Question 1

what type of molecules are PDGF-beta and Insulin receptor

Answer 1

RTK

Question 2

2 different way that PI3K can bind an RTK

Answer 2

binding to PDGF-beta, PI3K binds directly to receptor

with insulin, PI3K needs adapter protein

Question 3

what is the adaptor protein for PI3K binding to insulin receptor

Answer 3

IRS1

Question 4

3 key domains of IRS-1 protein

Answer 4

N terminal has PH domain which binds to PIP2
N terminal also has SH2 domain

both of these domains anchor IRS-1 to Insulin receptor

also YXXM sequence

Question 5

PIP2 and PIP3 bind what type of domains

Answer 5

PH domain

Question 6

what does PH domain stand for

Answer 6

plekstrin homology domain

Question 7

3 components of pip2

Answer 7

lipid, phosphate, inositol

Question 8

SH2 stands for

Answer 8

Src homology domain 2

Question 9

what happens at YXXM sequence

Answer 9

tyrosine is phosphorylated - this is substrate for the tyrosine kinase domain of the insulin receptor

Question 10

what happens to IRS when tyrosine is phosphorylated to phosphotyrosine

Answer 10

IRS serves as adaptor protein, linking insulin receptor to downstream signalling events

Question 11

difference between pip2 and pip3

Answer 11

PIP3 has one extra phosphate group at carbon 1 - phosphate instead of hydroxyl

Question 12

what molecule is responsible for the pip2 to pip3 transition

Answer 12

pi3k

Question 13

what kind of family is PI3K in

Answer 13

lipid kinases

Question 14

structure of PI3k molecule

Answer 14

heterodimer of 2 subunits of 110 kDa and 85kD

Question 15

what are the 2 monomers in PI3K

Answer 15

catalytic monomer called p110, and regulatory monomer called P85

Question 16

what 2 things mediate the activation of PI3K

Answer 16

SH2 domain of P85 interacting with phosphorylated RTK

P110 subunit associating with Ras-GTP

Question 17

2 other key domains of PI3K

Answer 17

ABD, RBD, Kinase

Question 18

ABD domain of PI3K

Answer 18

adapter protein binding domain - this is responsible for binding the regulatory domain (p85)

Question 19

RBD domain of PI3K

Answer 19

receptor binding domain of PI3K - binds to Ras

Question 20

3 domains of p85 (PI3K)

Answer 20

cSH2 domain, I, and N

I means inter-SH2

Question 21

state of p110 and p85 when inactive

Answer 21

bound together

carboxyl side of sh2 domain blocks kinase domain - making it inactive

Question 22

how is PI3K activated

Answer 22

when RTK is activated and tyrosine is phosphorylated, the N-sh2 and C-sh2 bind to the phosphorylated tyrosine

means cSH2 is no longer blocking the active site, and active site is available

Question 23

what does active PI3K target

Answer 23

PIP2 (inositol)

Question 24

what is PTEN

Answer 24

PTEN catalyses reverse reaction of PIP3-> PIP2

Question 25

what kind of molecule is PTEN

Answer 25

phosphatase

Question 26

what does pip3 actiate

Answer 26

PDK1

Question 27

what special domain does PDK1 have

Answer 27

pleckstrin homology domain which is specific for pip3

Question 28

what happens once you have a lot of PIP3

Answer 28

you’ll draw other proteins that bind PIP3

Question 29

what are PIP3 binding proteins

Answer 29

Akt/PKB, also PDK1,

Question 30

where do PDK1 and AKT bind to PIP3

Answer 30

on membrane

Question 31

what happens once PDK1 and AKT bind PIP3

Answer 31

Activated PDK phosphorylates AKT at Thr308

Question 32

what 2 residues on AKT need to be phosphorylated to be active

Answer 32

thr308 and serine 473

Question 33

what molecule phosphorylates AKT at Sea 473

Answer 33

other proteins like MTORC2

Question 34

what happens once AKT is phosphorylated on both residues

Answer 34

it leaves the membrane -> goes to activate other substrates