26_Signal Transduction IV

Question 1

What is an example of a cytoplasmic protein-tyrosine kinase?

Answer 1

Jak

Question 2

In (ligand/receptor)-mediated dimerization, each RTK chain binds a distinct ligand, while in (ligand/receptor)-mediated dimerization, a single ligand binds to two binding sites

Answer 2

receptor-mediated

ligand-mediated

Question 3

How do RTKs phosphorylate?

Answer 3

trans-autophosphorylation

each chain possesses a kinase domain; once dimerized, these domains cross-phosphorylate

Question 4

The tyrosine kinase domain is on the (extracellular/cytoplasmic) side of an RTK.

Answer 4

cytoplasmic

Question 5

Contrast the extracellular side of EGF receptors, insulin receptors, and PDGF receptors.

Answer 5

• Insulin receptor dimers are connected by disulfide bridges.
• EGF receptors have cysteine-rich domains outside the cell
• PDGF receptors have Ig-like domains.
• Insulin receptors are composed of two subunits (a and b).

Question 6

Where are the a and b subunits of the insulin receptor located? How are they joined?

Answer 6

a subunits are entirely extracellular, while b subunits are transmembrane.
They are connected via disulfide bridges.

Question 7

What is the function of autophosphorylation sites on RTKs?

Answer 7

• regulate kinase activity (increase)

- docking sites for signalling molecules

Question 8

What are the two domains that can bind phosphorylated tyrosines?

Answer 8

SH2 (Src homology domain 2)

PTB (phosphotyrosine-binding domain)

Question 9

What do SH3 domains bind?

Answer 9

hydrophobic proline residues

Question 10

Grb2 is an example of a (adaptor protein/docking protein/TF/signalling enzyme).

Answer 10

adaptor protein

Question 11

Grb2 interacts with the RTK via its _____ domain.

Answer 11

SH2

Question 12

Which is a docking protein?

Grb2, Sos, Jun, IRS, Shp2, PI3K, PLC

Answer 12

IRS

Question 13

Shp2 is a (phosphatase/kinase).

Answer 13

phosphatase

Question 14

IRS interacts with an RTK via its ____ domain.

Answer 14

PTB

Question 15

Which accessory protein activates G-proteins? How does it function?

Answer 15

GEF (guanine-nucleotide exchange factor): stimulates exchange of GDP for GTP

Question 16

How do GAPs modulate G-protein activity?

Answer 16

GAP = GTPase-activating protein

inactivates by stimulating hydrolysis of GTP to GDP

Question 17

Which accessory protein inhibits release of GDP?

Answer 17

GDIs (guanine nucleotide-dissociation inhibitors)

Question 18

Mutations in human Ras prevent _________ and mutant Ras remains in the (ON/OFF) position.

Answer 18

GTP hydrolysis

ON

Question 19

IRS is a docking protein that helps recruit both a kinase and a phosphatase. What are they?

Answer 19

kinase: PI3K
phosphatase: Shp2

Question 20

What domain do signalling enzymes use to dock to RTKs?

Answer 20

SH2

Question 21

What is the effector of Ras in the MAP kinase cascade?

Answer 21

Raf kinase

Question 22

What is the adaptor protein in the MAP kinase cascade?

Answer 22

Grb2

Question 23

What is the role of Sos in the MAP kinase cascade?

Answer 23

GEF

Question 24

What is the final protein to be phosphorylated in the MAPK cascade?

Answer 24

a TF

e.g. Fos & Jun

Question 25

How does phosphorylation affect the location of Raf?

Answer 25

Inactive Raf is soluble; once phosphorylated, it becomes membrane-bound.

Question 26

What is the significance of MKP-1 transcription in the MAPK cascade?

Answer 26

MKP-1 is a MAPK phosphatase. It will act as a phosphatase and will inactivate ERK, thereby turning the cascade OFF.

Question 27

How does PKA affect Raf?

Answer 27

It phosphorylates Raf, thereby inactivating it.

Question 28

Where do the MAPK and epinephrine signalling pathways converge?

Answer 28

At Raf