RTK and Ras

Question 0

Ligand of receptor tyrosine kinases

Answer 0

Peptide growth hormones

Question 1

Growth factors use what type of receptor?

Answer 1

Receptor tyrosine kinases

Question 2

Function of receptor tyrosine kinases

Answer 2

Mediate cell growth and differentiation

Question 3

RTKs promote what?

Answer 3

Cell growth and differentiation

Question 4

Signaling molecule in a RTK leads to…

Answer 4

Dimerization of two RTKs and cross-phosphorylation. The RTK is now activated and intracellular signaling proteins now bind to the phosphorylated tyrosine on the RTK

Question 5

What domain is phosphorylated on RTKs?

Answer 5

The tyrosine kinase domain

Question 6

What recognition domain typically binds to active RTK?

Answer 6

SH2 domains

Question 7

What is Src?

Answer 7

First nonreceptor Tyrosine kinase discovered.. Mutations lead to activation of the kinase activity leading to cancer. Has SH2 domain.

Question 8

What type of molecule is Ras? Function?

Answer 8

Small GTPase responsible for cell growth, differentiation, and migration in response to extracellular signals

Question 9

Method of action of Ras?

Answer 9

Transmit signals from the tyrosine kinases at the plasma membrane to serine/threonine kinases which then deliver signal to the cell nucleus

Question 10

Detail mechanism of RTK and Ras activation

Answer 10

EGF (ligand for example) dimerize RTK leading to autophosphorylation. GRB2 and SOS couple inactive Ras to the RTK. SOS promotes loss of GDP on Ras and addition of GTP which now active Ras

Question 11

What type of molecule is SoS??

Answer 11

A guanine nucleotide exchange factor (GEF)

Question 12

Ras is made active via?

Answer 12

A GEF (like SOS) which dissociates GDP and adds GTP to activate Ras

Question 13

How is Ras turned off?

Answer 13

A GAP (GTPase-activating protein) dephosphorylates GTP on Ras to GDP making it inactive

Question 14

Function of GAP?

Answer 14

Facilitates GTP hydrolysis by Ras

Question 15

Describe the Ras MAP kinase pathway

Answer 15

Activated Ras activates Map KKK which Ps MAP KK which Ps MAP K which then leads to P of proteins for complex change in behavior

Question 16

T or F: There are multiple MAP kinase pathway leading to many outcomes

Answer 16

T

Question 17

T or F: MAPK regulates Tx factors in the nucleus

Answer 17

T

Question 18

Neuro-Cardio-Facial-Cutaneous (NCFC) syndromes are caused by what mutation?

Answer 18

Ras pathway mutation e.g. Costello or Noonan syndrom

Question 19

Ras mutations lead to what general disease?

Answer 19

Oncogenesis, cognition, growth, and development disease.

Question 20

Detail the RTK and MAPK interaction

Answer 20

RTK activates Ras which activates MAPK (RTK to Ras can also activate PI3K)

Question 21

What does PI 3-kinase act on?

Answer 21

Phosphorylates inositol phospholipids (very rare to P a lipid). Can take PI to PIP2 (up to PIP3)

Question 22

What is the function of PI 3-kinase?

Answer 22

Promotes cell survival

Question 23

Detail the mechanism of PI 3-kinase activity

Answer 23

Activated by RTK takes PIP2 to PIP3 which activates PKB which Ps Bad leading to inhibition of apoptosis

Question 24

What is PTEN? Relation to PI 3-kinase?

Answer 24

PTEN promotes cellular apoptosis by preventing RTK activation of PI 3-kinase

Question 25

PTEN is what type of factor?

Answer 25

Tumor suppressor (causes apoptosis)

Question 26

What does PI 3-Kinase interact with to become activated?

Answer 26

Ras on an RTK directly via SH2 domain binding

Question 27

What sort of signals activate PI 3-kinase activity?

Answer 27

Proliferation, differentiation, cell survival, and cytoskeletal reorganization

Question 28

Effector of Gs

Answer 28

PKA

Question 29

Effector of Gq?

Answer 29

CaM-Kinase or PKC

Question 30

Effector of RTK

Answer 30

Phospholipiase C (PKC) or Ras (MAP-kinase) or PI-3K (PKB)

Question 31

Insulin receptor activity detail

Answer 31

Activates an RTK which leads to PI-3kinase activity leading to activation of PKB and activation of Glut4