Exam 2 Receptor Tyrosine Kinases

Question 1

Four general characteristics of receptor tyrosine kinases

Answer 1

1. They are membrane-bound receptor complexes that transduce extracellular signals
2. Have endogenous protein kinase activity and directly activate downstream pathways
3. Have two domains - an extracellular ligand binding domain and a cytoplasmic active site
4. Cytoplasmic active site phosphorylates Tyr residues for receptor proteins

Question 2

Explain the steps of the insulin receptor pathway.

Answer 2

1. Insulin receptor binds insulin and undergoes autophosphorylation on its carboxyl-terminal Tyr residues
2. Insulin receptor phosphorylates IRS-1 on its Tyr residues
3. SH2 domain of Grb2 binds to P-Tyr of IRS-1. Sos binds to Grb2, then to Ras, causing GDP release and GTP binding to Ras
4. Activated Ras activates Raf-1
5. Raf-1 phosphorylates MEK on two Ser residues, activating it. MEK phosphorylates ERK on a Thr and Tyr residue, thus activating it
6. ERK moves into the nucleus and phosphorylates nuclear transcription factors such as ELK1
7. Phosphorylated ELK1 joins SRF to stimulate the transcription and translation of a set of genes needed for cell division

Question 3

Ras phosphorylates

Answer 3

Raf-1

Question 4

Raf-1 phosphorylates

Answer 4

MEK

Question 5

MEK phosphorylates

Answer 5

ERK

Question 6

MEK and ERK are both phosphorylated at a

Answer 6

Thr or Tyr residue

Question 7

ERK can enter the nucleus and phosphorylate transcription factors such as

Answer 7

Elk-1

Question 8

What does MAPK stand for, and what is it’s purpose?

Answer 8

Mitogen-activated protein kinase; amplifies signals and initiates growth factors

Question 9

What are mitogens?

Answer 9

Chemicals that stimulate mitosis and cell growth

Question 10

Raf-1 is which type of MAP kinase?

Answer 10

MAP kinase kinase kinase

Question 11

ERK is which type of MAP kinase?

Answer 11

MAP kinase

Question 12

MEK is which type of MAP kinase?

Answer 12

MAP kinase kinase

Question 13

Kinases of the MAPK and MAPKKK families phosphorylate which type of residues?

Answer 13

Serine or Threonine

Question 14

Kinases of the MAPKK families phosphorylate which type of residues?

Answer 14

Serine and Tyrosine

Question 15

Describe the pathway where IRS-1 interacts with phosphoinositide 3-kinase (PI3K)

Answer 15

1. IRS-1 activates PI3K by binding to its SH2 domain. PI3K converts PIP2 to PIP3
2. PKB bound to PIP3 is phosphorylated by PKD1, which activates it, and deactivates GSK3 (which normally turns off glycogen synthase, but since in the presence of insulin, we want glycogen synthase to be on)
3. Inactive GSK3 cannot phosphorylate glycogen synthase (GS), so it stays active.
4. Synthesis of glycogen from glucose is accelerated
5. PKB stimulates movement of glucose transporter GLUT4 from internal membrane vesicles to plasma membrane so the cell can increase uptake of glucose

Question 16

IRS-1 binds to

Answer 16

PI3K

Question 17

IRS-1/PI3K converts

Answer 17

PIP2 to PIP3

Question 18

Protein kinase B (PKB) binds to

Answer 18

PIP3

Question 19

PKD-1 phosphorylates

Answer 19

PKB

Question 20

PKB then phosphorylates

Answer 20

GSK3

Question 21

When GSK3 is phosphorylated, it is turned (on / off)

Answer 21

Off

Question 22

Glycogen synthase (GS) is then turned (on / off)

Answer 22

On

Question 23

GSK3 is normally (unphosphorylated / phosphorylated) and (inactive / unactive).

Answer 23

GSK3 is normally unphosphorylated and active

Question 24

When GSK3 is active, this means that glycogen synthase (GS) is (active / inactive)

Answer 24

Inactive

Question 25

When protein kinase B (PKB) is activated, it causes which type of movement of of the GLUT4 transporter?

Answer 25

Clathrin-dependent movement

Question 26

What happens when GLUT-4 moves to the plasma membrane?

Answer 26

Starts taking up glucose from the blood

Question 27

Many tyrosine kinase receptors are in the ________ _________. The JAK-STAT pathway employs a soluble receptor tyrosine kinase which means it is in the _________.

Answer 27

Plasma membrane; cytosol