Lodish 8e Ch16 Test Bank PDF

16 - 10 16 Signaling Pathways That Control Gene Activity Section 16.1 1. Latent TGF is converted to mature TGF by: a. dephosphorylation. b. phosphorylation. c. proteolysis. d. translocation. e. none of the above Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering...

16 - 10 16 Signaling Pathways That Control Gene Activity Section 16.1 1. Latent TGF is converted to mature TGF by: a. dephosphorylation. b. phosphorylation. c. proteolysis. d. translocation. e. none of the above Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 2. A loss-of-function mutation in which of the following would inhibit TGF signaling? a. I-Smad b. R-Smad c. Ski d. SnoN e. all of the above Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 3. A gain-of-function mutation in which of the following would promote malignancy in cells whose proliferation is inhibited by TGF ? a. co-Smad b. I-Smad c. R-Smad d. all of the above e. none of the above Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 4. Which of the following receptors binds TGF ? a. type I b. type II c. type III d. types I and II e. types II and III Ans: e Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Moderate 5. What feature allows TGF signaling molecules to be quickly mobilized? Ans: TGF signaling molecules are secreted and stored in the extracellular matrix in an inactive form. When needed, they can be rapidly activated by proteolytic digestion. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Moderate 6. Ski and SnoN were originally identified as oncoproteins. Explain how constitutive expression of these proteins promotes cancer. Ans: Ski and SnoN both inhibit TGF signaling by binding to nuclear Smad complexes and preventing these complexes from modulating expression of target genes. Because TGF signaling inhibits the proliferation of many cells, constitutive expression of Ski and SnoN would render cells insensitive to this antiproliferative signal, leading to unregulated cell division. Question Type: Essay Chapter: 16 Blooms: Applying Difficulty: Moderate 7. TGF-β normally promotes: a. cell division. b. cell motility. c. tissue organization. d. all of the above Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy Section 16.2 8. 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 Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 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 Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Moderate 10. Compare and contrast the mechanisms by which SHP1 and SOCS proteins modulate erythropoietin signaling. Ans: SHP1 and SOCS are both induced by negative feedback loops to down-regulate erythropoietin signaling. SHP1 is a phosphatase that contains SH2 domains that bind to activated erythropoietin receptors (EpoR). SHP1 bound to EpoR induces short-term down-regulation by dephosphorylating and inhibiting JAKs. SOCS proteins also contain SH2 domains that bind EpoR to prevent the binding of signaling molecules, bind the activation lip of JAKs to inhibit their activity, and recruit ubiquitin ligases to target JAKs for degradation. Degradation of JAKs leads to long-term down-regulation. Question Type: Essay Chapter: 16 Blooms: Applying Difficulty: Difficult 11. 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 Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Easy Section 16.3 12. The EGF receptor is a(n): a. adapter protein. b. guanine nucleotide exchange protein. c. kinase. d. protease. e. none of the above Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 13. 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. Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Moderate 14. 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 Ans: a Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Moderate Section 16.4 15. Ras is a(n): a. adapter protein. b. guanine nucleotide exchange factor. c. kinase. d. protease. e. none of the above Ans: e Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Easy 16. 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 Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 17. Serum response factor (SRF) is phosphorylated by: a. MEK. b. MAP kinase. RSK c. p90. d. Raf. e. Ras. Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 18. Describe the role of adapter proteins in the activation of Ras by receptor tyrosine kinases. Ans: Following dimerization and autophosphorylation of receptor tyrosine kinases, GRB2 and Sos proteins couple the receptor to the inactive Ras·GDP complex. Sos promotes dissociation of GDP from Ras, allowing GTP to bind. Sos acts as a guanine nucleotide exchange factor (GEF), which helps convert inactive Ras·GDP to active Ras·GTP. The Ras·GTP complex can then activate downstream effector molecules. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Moderate 19. Describe the mechanism by which Ras is cycled from its active to inactive form. Ans: Ras is cycled from its active to inactive form by the action of two proteins: guanine nucleotide exchange factor (GEF) and GTPase activating protein (GAP). When bound to GDP, Ras is in its inactive form. Binding of GEF to the Ras·GDP complex causes release of GDP and binding of GTP. Ras bound to GTP is in its active form. The active Ras·GTP complex possesses low intrinsic GTPase activity, which is elevated when GAP binds, causing conversion to inactive Ras·GDP. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Moderate 20. Describe the experimental approach used to determine the order of events in a signaling pathway. Ans: The order of events in a signaling pathway can be determined by the analysis of mutants. For example, quiescent cells can be induced to proliferate in the absence of growth factors if they contain a constitutively active mutant Raf protein. In addition, cells that express a mutant defective Raf protein cannot be stimulated to proliferate uncontrollably by in the presence of a constitutively D active Ras protein. These results show that Ras is upstream of Raf in the signaling pathway. Question Type: Essay Chapter: 16 Blooms: Applying Difficulty: Moderate 21. How can multiple MAP kinase pathways be segregated when they share a common component? Ans: Despite different MAP kinase pathways sharing common components, they are able to avoid cross talk between pathways. This is accomplished by formation of pathway-specific complexes assembled on molecular scaffolds. In this way, a specific component can be present in more than one MAP kinase pathway but will only result in one specific signaling pathway because it is complexed with a set of pathway-specific components. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Moderate 22. Explain why, upon ligand binding, cell-surface receptors are often subjected to receptor-mediated endocytosis. Ans: Removal of transmembrane receptors by receptor-mediated endocytosis is one mechanism to down-regulate receptor signaling so that the signal is not too robust and does not persist long after the signaling molecule is removed. Receptors that are endocytosed may eventually be recycled back to the cell surface, but this takes time. They may even be degraded in lysosomes, an even longer-term mechanism for down-regulation of signaling. Question Type: Essay Chapter: 16 Blooms: Applying Difficulty: Moderate 23. 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. Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Moderate 24. 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. Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Easy 25. 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. Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Applying Difficulty: Easy 26. 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. Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 27. 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. Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Moderate 28. The order of events in a signaling pathway can be determined by the analysis of mutants. Cells that express a mutant defective D Raf protein cannot be stimulated to proliferate uncontrollably by constitutively active Ras (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. Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 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 Ans: a Question Type: Multiple choice Chapter: 16 Blooms: Understanding Difficulty: Easy 30. 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. Ans: d Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Moderate 31. Which protein stabilizes an intermediate in the Ras GTP hydrolysis reactions? a. Sos b. GRB2 c. RTK d. Raf Ans: a Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy Section 16.5 32. 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 Ans: e Question Type: Multiple choice Chapter: 16 Blooms: Applying Difficulty: Moderate 33. 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 Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Moderate 34. 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 Ans: e Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 35. How does activation of protein kinase B promote cell survival? Ans: Protein kinase B phosphorylates and inhibits Bad and other pro-apoptotic proteins. Protein kinase B also phosphorylates the transcription factor Forkhead-1, which results in Forkhead-1 binding to 14-3-3 and becoming sequestered in the cytosol where it cannot activate pro-apoptotic genes. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Moderate 36. 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? Ans: The activation lip is a region in the protein kinase containing one or more amino acids that must be modified by phosphorylation to induce a conformational change that activates the kinase. Question Type: Essay Chapter: 16 Blooms: Understanding Difficulty: Easy Section 16.6 37. All genes regulated by PKA contain a cis-acting DNA sequence that binds to the phosphorylated form of a transcription factor called: a. -catenin. b. CREB. c. c-Jun. d. TCF. Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 38. Predict the consequences of a temperature-sensitive mutation in which phosphorylation of the -catenin protein is blocked. Above the permissive temperature: a. -catenin levels will increase and -catenin will be constitutively active. b. -catenin levels will increase and -catenin will be inactive. c. -catenin levels will decrease. d. -catenin will remain constant but cells will be unresponsive to Wnt signaling. Ans: a Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Easy 39. In the NF- B signaling pathway, which of the following molecules is downstream of I- B kinase? a. NF- B b. TAK1 c. TNF- d. NF- B and TAK1 e. all of the above Ans: a Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 40. 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? Ans: All genes regulated by PKA contain a cis-acting DNA sequence called the CRE (cAMP response element.) Activated PKA phosphorylates the CREB protein. Together with the co-activator, CBP/300, phosphorylated CREB protein can bind to CRE sequences of target genes to activate transcription. Reference for the research cited in this question: Asher, O., et al. 2002. Ethanol stimulates cAMP-responsive element (CRE)- mediated transcription via CRE-binding protein and cAMP-dependent protein kinase, J. Pharmacol Exp Ther. 301(1): 66–70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11907158&dopt=Abstract Question Type: Multiple choice Chapter: 16 Blooms: Analyzing Difficulty: Difficult Section 16.7 41. Which of the following is cleaved by regulated intramembrane proteolysis (RIP)? a. I B b. Notch c. TGF d. I B and TGF e. Notch and TGF Ans: b Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 42. NF- B signaling is important in: a. development. b. immunity. c. inflammation. d. immunity and inflammation. e. all of the above Ans: c Question Type: Multiple choice Chapter: 16 Blooms: Remembering Difficulty: Easy 43. What feature distinguishes the ligand Delta from other ligands such as EGF, TGF , and erythropoietin that bind transmembrane receptors? Ans: The other ligands are diffusible molecules that can travel some distance from the cell that secretes the ligand to the cell that expresses the receptor. In contrast, Delta is a transmembrane protein and therefore must be expressed on a cell that is in direct contact with the target cell expressing the receptor Notch. Question Type: Essay Chapter: 16 Blooms: Applying Difficulty: Moderate