Human Anatomy & Physiology (11th Edition)
11th Edition
ISBN: 9780134580999
Author: Elaine N. Marieb, Katja N. Hoehn
Publisher: PEARSON
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- A pharmaceutical company developed a drug, CP788, that inhibits the interaction of Grb2 with SH2 domains as a treatment for breast cancer. As the data below shows, the compound inhibits activation of RAS in MDA-MB-468 breast cancer cells (Figure A) and anchorage-dependent growth (Figure B solid line) in MDA-MB-468 breast cancer cells. Note that these experimets were done in the presence of EGF. Briefly explain the steps in the pathway by which inhibition of Grb2/SH2 interaction would inhibit activation of RAS (limit 5-6 sentences). A Inhibition of RAS Activation by CP788 % RAS Activation 120 100 80 60 20 0 0 50 [CP788] UM 100 B Colonies number (% of untreated control) 120 100 80 60 40 20 0 10-² HigHt 10-¹ 10⁰ 10¹ 10² 10³ [CP788] UMarrow_forwarddo you have any clues? GAP protein helps hydrolyze the GTP to GDP in RAS protein. Argenine 789 residue in GAP protein interacts with GTP in RAS protein. However, Arg 789 is mutated to Alanine. which are true or false? ____We expect Ala789 GAP to have no consequence for cell growth or survival signaling. ____Arg789 stabilizes the T-loop of GAP in the outward (active) position, so we expect Ala789 GAP to have no kinase activity. ___Arg789 participates in the GTP hydrolysis reaction carried out by RAS, so we expect RAS to be catalytically inactive when partnered with Ala789 GAP. ____Arg789 binds in the major groove of the DNA double helix, so we expect Ala789 GAP to be inactive as a transcriptional regulator. __Arg789 interacts with RAS switch 1 and switch 2 regions, so we expect the RAS switch to fail with Ala789 GAP. ____The RAS switch would be locked in the OFF position by Ala789 GAP, so we expect no constitutive RAS signaling and hence no risk of this tumor metastasizing. ____The…arrow_forwardA temperature-sensitive mutant allele of Ras causes the Ras protein to be fixed in the GDP-bound state at the nonpermissive temperature. What phenotype would you expect a cell homozygous for this mutation to have at the nonpermissive temperature? A.) It would stop dividing. B.) It would divide continuously. C.) It would divide normally.arrow_forward
- Which of the following is NOT an example of allosteric regulation? Select an answer and submit. For keyboard navigation, use the up/down arrow keys to select an answer. a Phosphorylation of the CTD of RNA polymerase II. b с d Lactose binding to the Repressor protein. GTP binding to elF2. CAMP binding to cAMP protein-dependent kinasearrow_forwardYou isolated two mutant cells (Cell A and Cell B) which have a problem in the signal transduction pathway. Both cells show activated response to one of RTK mediated signaling without ligand, suggesting the signaling pathway has been constitutively activated by mutations. You introduced mutant Ras that blocks Ras activation step in both cells. When the mutant Ras was expressed in cell A, the signaling pathway was no longer activated. On the other hand, when the mutant Ras was expressed in cell B, the signaling pathway was still active. From these results; Q1) Which protein of the signaling pathway in Cell A might have the mutation? How does that mutation affect the function of that protein? Why do you think so? Q2) Which protein of the signaling pathway in Cell B might have the mutation? How does that mutation affect the function of that protein? Why do you think so?arrow_forwardWhich of the following mutations would produce a form of the Ras protein that would be more difficult to inactivate than normal Ras? Briefly explain your reasoning.(i) A mutation that allows Ras to cleave (hydrolyze) GTP more rapidly than usual(ii) A mutation that causes Ras to bind Ras-GAP more tightly than usual(iii) A mutation that causes Ras to cleave (hydrolyze) GTP more slowly than usualarrow_forward
- A growth factor Fsh3 stimulates the proliferation of culture fish cells. The receptor that binds Fsh3 is a receptor tyrosine kinase (RTK) and there are numerous fish tumor cell lines that have a mutation for the gen for this receptor. Which of the following mutations would be expected to promote uncontrolled cell proliferation. a mutation that inactivates the protein tyrosine phosphatase that acts on the receptor a mutation that prevents the binding of the normal extracellular signal to the receptor a mutation that inhibits the Ras GEF a mutation that destroys the kinase activity of the receptor a mutation that prevents dimerization of the receptorarrow_forwardYou established two cell lines (Cell line X and Cell line Y) from colon cancer patients and both of them can proliferate without the Wnt ligand. When you analyze the tumor suppressor APC (Adenomatous Polyposis Coli) protein in these lines, X does not express functional APC but Y expresses functional APC. How can Y keep proliferating without Wnt? Which function (protein) within the Wnt signaling pathway might be defective in Y?arrow_forwardWhich arrestin is required for activation of phosphorylation of MDM2 during chronic Iso stimulation? use the following Figures 1and 2 respectively to explain pleasearrow_forward
- You are studying a pathogenic bacterium which secretes a toxin that affects G protein receptor signaling. You perform a preliminary experiment in which you examine intracellular CAMP levels in untreated and toxin treated cells. The data is in the figure below. How does the toxin affect CAMP levels due to G protein receptor signaling? Select all that apply CAMP levels 250 200 150 100 50 0 no Toxin with Toxin The toxin stimulates GTP binding to the Gas subunit The toxin stimulates GTP binding to the Gai subunit The toxin inhibits GAP or GTPase activating proteins The toxin stimulates adenylyl cyclase activityarrow_forwardYou stimulated the cell with a ligand and analyzed the response. Upon ligand treatment, the cell increased the expression of gene α and decreased expression of gene β. When you inhibit cyclic AMP production by treating the cell with an inhibitor of Adenylyl cyclase, the increased expression of gene α was not observed but the decrease gene β expression was still observed. a) What you can expect for gene α regulation by this ligand? What signaling mechanism could be used? b) To determine how gene β is regulated by the ligand via what signaling mechanism, provide your hypothesis and indicate a potential experiment that you can perform to test that.arrow_forwardHerceptin is an antibody that is used to treat certain forms of breast cancer by binding to a class of estrogen receptors. What is the basis for its effectiveness in treating certain forms of breast cancer?arrow_forward
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