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MG5607 Practice2 – AU14 Page 1 of 3 MULTIPLE CHOICE QUESTIONS Each question in this section is worth 3 points. For full credit, choose only one of the possible answers. Alternatively, you may choose two answers and if one of them is correct you will receive 1.5 points for that question. 1) Indicate what would happen to the Ras pathway if you expressed an altered Ras-GEF protein that has a lipid group, known as myristic acid, attached to its N-terminus. a) there would be no effect because the Ras-GEF is already a membrane-associated protein b) this would result in the stimulation of the intrinsic GTPase activity associated with the Ras proteins and the down-regulation of this signaling pathway c) this would result in the artificial recruitment of the Ras-GEF protein to the plasma membrane and in the elevated activation of the Ras pathway d) this would interfere with receptor tyrosine kinase dimerization and thus decrease signaling through the Ras pathway e) the presence of this protein would titrate out the available GTP and thereby result in decreased signaling through the Ras pathway 2) Indicate which of the following best describes the signal on/in cells undergoing apoptosis that is responsible for their uptake by phagocytic cells. a) the release of cytochrome c from the intermembrane space within the mitochondria b) the presence of abnormal membrane blebbing at the cell surface c) the presence of the Fas death receptor in the plasma membrane that can interact with the Fas ligand on the surface of nearby phagocytic cells d) the presence of phosphatidylserine in the outer leaflet of the plasma membrane e) the loss of integrity of the nuclear envelope and the subsequent fragmentation and release of chromosomal DNA 3) Indicate what would happen if you over-expressed, in wild-type cells, a mutant version of the PDGF receptor that is defective for ligand binding. a) this mutant would form nonproductive complexes with the normal downstream effectors of PDGFR and thus diminish normal PDGF signaling b) this mutant would form defective dimers with the wild-type receptor and lead to diminished signaling by PDGF c) the presence of additional PDGF receptors at the cell-surface would lead to increased PDGF binding and elevated levels of downstream signaling d) the over-expression of this mutant receptor would have no significant effect upon PDGF signaling e) the presence of this mutant would result in a failure to down-regulate the wild-type pathway by receptormediated endocytosis and would thus lead to elevated levels of PDGF signaling MG5607 Practice2 – AU14 Page 2 of 3 ESSAY-FORMAT QUESTIONS 4) (5 pts.) Many human tumors contain Ras mutations that result in the production of a constitutively-active version of the Ras protein. Given that Ras activates the ERK MAP kinase cascade, Dr. Brutus has decided to treat these tumors with a drug that inhibits the ERK enzyme. Indicate below whether you think this approach would be successful (fully, partially or not at all) for these types of tumors. Please explain your answer. 5) (6 pts.) We discussed two types of “cancer-critical” genes: the proto-oncogenes and the tumor suppressor genes. For parts a & b, indicate whether the cancer-causing mutations are activating or inactivating for each class of gene. (a) For tumor suppressor genes (1 pt.): ________________________________ (b) For proto-oncogenes (1 pt.): ________________________________ For parts c & d, give one example of each class of gene and briefly describe how alterations of the encoded product contribute to cancer progression. (c) Tumor suppressor gene (2 pts.): (d) Proto-oncogene (2 pts.): MG5607 Practice2 – AU14 Page 3 of 3 6) (5 pts.) A mutation that changes Tyr771 in the PDGF receptor to an alanine results in a loss of the PDGF-mediated activation of a Ras-GAP. However, this alteration does not prevent the PDGF-mediated activation of phospholipase C-γ (PLC). Describe how this Tyr771-to-Ala (Y771A) alteration could have different effects upon these two downstream targets of PDGF signaling. ______________________________________________________ 7) BONUS QUESTION (2 pts.) Although a particular yeast responds very differently to two secreted pheromones, X1 and X2, it has been found that both pheromones activate the same MAP kinase kinase kinase enzyme, MKKK1. Given what you know about MAP kinase cascades, explain how these two pheromones could have such different effects.