Deck 15: Signaling Pathways That Control Gene Activity

Question 1

Which of the following is a protein kinase?

A)EGF receptor
B)erythropoietin receptor
C)STAT5
D)EGF receptor and erythropoietin receptor
E)all of the above

Answer 1

A

Question 2

The EGF receptor is a(n):

A)adapter protein.
B)guanine nucleotide exchange protein.
C)kinase.
D)protease.
E)none of the above

Answer 2

C

Question 3

Which of the following mechanisms is NOT used to terminate cytokine signaling and the JAK/STAT pathway?

A)transcription of SOCS proteins
B)dephosphorylation of phosphotyrosine residues
C)heterodimerization of cytokine receptors
D)receptor internalization

Answer 3

C

Question 4

A gain-of-function mutation in which of the following would promote malignancy in cells whose proliferation is inhibited by TGFβ?

A)co-Smad
B)I-Smad
C)R-Smad
D)all of the above
E)none of the above

Question 5

Latent TGFβ is converted to mature TGFβ by:

A)dephosphorylation.
B)phosphorylation.
C)proteolysis.
D)translocation.
E)none of the above

Question 6

Ras is a(n):

A)adapter protein.
B)guanine nucleotide exchange factor.
C)kinase.
D)protease.
E)none of the above

Question 7

Compare and contrast the mechanisms by which SHP1 and SOCS proteins modulate erythropoietin signaling.

Question 8

In which of the following double-mutant flies will R7 photoreceptors develop normally?

A)constitutively active Raf and inactive MAPK
B)constitutively active MAPK and inactive Ras
C)constitutively active Ras and inactive Raf
D)all of the above
E)none of the above

Question 9

Binding of erythropoietin to its extracellular receptor engages which of the following signaling pathways?

A)JAK/STAT
B)Ras/MAP kinase
C)PI-3 kinase
D)all of the above
E)none of the above

Question 10

What feature allows TGFβ signaling molecules to be quickly mobilized?

Question 11

Which of the following receptors binds TGFβ?

A)type I
B)type II
C)type III
D)types I and II
E)types II and III

Question 12

Ski and SnoN were originally identified as oncoproteins.Explain how constitutive expression of these proteins promotes cancer.

Question 13

Describe the mechanism by which Ras is cycled from its active to inactive form.

Question 14

Which of the following contain(s)an SH2 domain?

A)SHP1
B)SOCS
C)STAT5
D)all of the above
E)none of the above

Question 15

TGF- β normally promotes:

A)cell division.
B)cell motility.
C)tissue organization.
D)all of the above

Question 16

Binding of hormone to a receptor tyrosine kinase causes all of the following,except:

A)dimerization of the receptor.
B)autophosphorylation of the receptor.
C)activation of Ras through an interaction with GRB2 and Sos.
D)hydrolysis of GTP bound to Ras.

Question 17

Describe the experimental approach used to determine the order of events in a signaling pathway.

Question 18

Serum response factor (SRF)is phosphorylated by:

A)MEK.
B)MAP kinase.
C)p90ᴿˢᴷ.
D)Raf.
E)Ras.

Question 19

Describe the role of adapter proteins in the activation of Ras by receptor tyrosine kinases.

Question 20

A loss-of-function mutation in which of the following would inhibit TGFβ signaling?

A)I-Smad
B)R-Smad
C)Ski
D)SnoN
E)all of the above

Question 21

How does activation of protein kinase B promote cell survival?

Question 22

An SH2-containing protein contains a mutation that changes its binding pocket such that tyrosine and phosphotyrosine bind with equal affinity.As a result,MEK activity:

A)decreases due to changes in Raf activation.
B)decreases due to allosteric inhibition of SH2-domain binding.
C)increases with ligand binding-induced dimerization.
D)does not change with receptor dimerization and transautophosphorylation.

Question 23

Many kinases,including MAP kinase,protein kinase B,receptor tyrosine kinases,and JAKs,possess activation lips.What is an activation lip? What modification of the activation lip is required for activation of these kinases?

Question 24

Using a luciferase reporter system in tissue culture cells,researchers from the University of California,San Francisco,found that ethanol stimulates transcription of genes in brain cells possibly involved in the adaptive responses to alcohol.This process was found to depend on PKA activation.By analogy to other PKA-dependent transcription activation pathways,describe a possible pathway for this transcription induction.What other proteins would be involved?

Question 25

Which of the following are enzyme pairs that catalyze opposite reactions?

A)MEK and MAP kinase
B)NF-B and I-B
C)PI-3 kinase and PTEN phosphatase
D)JAKs and STATs
E)none of the above

Question 26

Many PTB-containing proteins act as docking sites for multiple proteins.If these proteins are involved in the RTK signal transduction pathway,they most likely:

A)contain GRB2 domains.
B)are involved in autophosphorylation of the RTK.
C)are phosphorylating the receptor and the docking protein.
D)are adopting a different conformation (shape)to expand the pathways affected by ligand binding.

Question 27

Which of the following signaling pathways can be activated by cytokines?

A)JAK/STAT
B)PI-3 kinase
C)Ras/MAP kinase
D)JAK/STAT and PI-3 kinase
E)all of the above

Question 28

Which protein stabilizes an intermediate in the Ras GTP hydrolysis reactions?

A)Sos
B)GRB2
C)RTK
D)Raf

Question 29

How can multiple MAP kinase pathways be segregated when they share a common component,like a downstream kinase?

A)formation of pathway-specific complexes assembled on molecular scaffolds
B)activation of different small G proteins
C)differential activation of activation lip tyrosines
D)phosphorylation of PTB-containing proteins

Question 30

Explain why,upon ligand binding,cell-surface receptors are often subjected to receptor-mediated endocytosis.

Question 31

All genes regulated by PKA contain a cis-acting DNA sequence that binds to the phosphorylated form of a transcription factor called:

A)β-catenin.
B)CREB.
C)c-Jun.
D)TCF.

Question 32

How can multiple MAP kinase pathways be segregated when they share a common component?

Question 33

Predict the consequences of a temperature-sensitive mutation in which phosphorylation of the β-catenin protein is blocked.Above the permissive temperature:

A)β-catenin levels will increase and β-catenin will be constitutively active.
B)β-catenin levels will increase and β-catenin will be inactive.
C)β-catenin levels will decrease.
D)β-catenin will remain constant but cells will be unresponsive to Wnt signaling.

Question 34

In the NF-B signaling pathway,which of the following molecules is downstream of I-B kinase?

A)NF-B
B)TAK1
C)TNF-α
D)NF-B and TAK1
E)all of the above

Question 35

Transcriptional activation downstream of the MAPK pathway involves:

A)MEK.
B)CREB phosphorylation.
C)binding of transcription factors to the SRE of c-Fos.
D)recruitment of Raf's N-terminal regulatory domain.
E)Ras activation upon Sos binding.

Question 36

Which of the following is NOT true about the role of adapter proteins in the activation of Ras by receptor tyrosine kinases?

A)Following dimerization and autophosphorylation of receptor tyrosine kinases,GRB2 and Sos proteins couple to the receptor.
B)GRB2 and Sos proteins couple the receptor to the inactive Ras·GDP complex.
C)GRB2 interacts with Sos via its SH3 domain.
D)Sos acts as a GAP,which helps convert Ras·GDP to active Ras·GTP.

Question 37

Before ligand binding,receptor tyrosine kinases:

A)contain binding sites for SH2-domain containing proteins.
B)contain activation lip tyrosines within the kinase active site.
C)bind to GRB2 within the cytosolic domains.
D)have excellent tyrosine kinase activity.

Question 38

By what mechanism does PI-3 phosphate promote activation of protein kinase B (PKB)?

A)recruiting PKB to the plasma membrane
B)recruiting the activating kinase PDK1 to the plasma membrane
C)releasing inhibition of the catalytic site by the PH domain
D)the first and second answers are correct
E)all of the above

Question 39

Which of the following explains why Ras is activated quickly by RTKs?

A)RTKs phosphorylate Ras.
B)Ras changes conformation upon ligand binding to prepare for activation.
C)Ras binds phosphotyrosine residues on RTKs.
D)Ras is maintained at the plasma membrane through a lipid-mediated attachment.

Question 40

The order of events in a signaling pathway can be determined by the analysis of mutants.Cells that express a mutant defective Raf protein cannot be stimulated to proliferate uncontrollably by constitutively active Rasᴰ (dominant active).This indicates:

A)quiescent cells can be induced to proliferate in the absence of growth factors if they contain a constitutively inactive mutant Raf protein.
B)Raf is upstream of Ras in the signaling pathway.
C)Ras is upstream of Raf in the signaling pathway.
D)Ras mutants are recessive to Raf mutants.

Question 41

NF-B signaling is important in:

A)development.
B)immunity.
C)inflammation.
D)immunity and inflammation.
E)all of the above

Question 42

What feature distinguishes the ligand Delta from other ligands such as EGF,TGFα,and erythropoietin that bind transmembrane receptors?

Question 43

Which of the following is cleaved by regulated intramembrane proteolysis (RIP)?

A)IB
B)Notch
C)TGFβ
D)IB and TGFβ
E)Notch and TGFβ