Chapter 16.3 learning activity key PDF

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Cell Biology 341 with Dr. Sally Pyle mandatory learning activity assignment key for chapter 16.3, has both questions and correct answers. ...

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Biol 341. 3-18-19: Ch 16.3 Learning Activity

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Manager ___________________ Recorder ___________________ Skeptic ___________________ 1. (4 points) Pictured below is the HER2/HER1-4 signaling pathway. About 20% of all breast cancers overexpress the HER2 (Human epidermal growth factor receptor-2) Receptor Tyrosine Kinase. Overexpression of the receptor in turn activates the signaling pathway causing the cells to divide without control. HER2 antibodies are used as a treatment for this subset of breast cancers and works well in these cases. Using the signaling pathway shown here, answer the following questions. Be sure to explain your answers, when asked.

a. Which portion of the signaling pathway would be involved in cell division? The pathway activated by HER2, since RAS is a protooncogene, that is involved in cell proliferation. b. How does activation of both HER2 and HER1-4 work to inhibit apoptosis? AKT is activated by these pathways, it in turn activates Bcl-2, which inhibits apoptosis. c. Why would an anti-HER2 antibody be a useful treatment for HER2 positive breast cancers? The antibody would bind to the receptor, but not activate the receptor, instead it would block the ligand from binding and would stop cell division. d. In HER2 positive breast cancers the gene is amplified and the receptor is overexpressed. Knowing this would you expect the anti-HER2 antibody to have side effects involving other tissues? Explain your answer.

Antibodies are very specific, so the anti-HER2 antibody would only bind these receptors, so no other side effects. 2. (3) The signaling pathway below is a simplified (yes, it is simplified) example of the interactions of various signaling pathways from a mammalian cell. This simplified cell has RTKs, GPCRs, cytokine receptors, death receptors, and even extracellular matrix signaling proteins, that act as signal transducers. For this question please make the following assumptions: Only activation of MEKK, MAPK, or PKA can initiate Cell Proliferation. Please use this diagram to help you answer the following questions.

a. You treat this cell with a drug that inhibits Ras so it cannot be activated. Now you treat the cell with Endothelial growth factor (EGF) and Insulin growth factor-1 (IGF1) – assume no other factors are interacting with the cell. After these treatments will the cell be able to initiate cell division? Explain please. EGF treatment wouldn’t initiate cell division, since it uses the Ras pathway, but IGF-1 uses the PKCNGkB pathway to initiate cell division which doesn’t need Ras, so you would start cell division. b. Identify a step, in either an RTK or GPCR signaling pathway, where you would expect to find amplification through production of a second messenger, and identify what second messenger would be produced (please note: second messengers aren’t shown here, but you should recognize the enzymes that would produce second messengers – we discussed these before break, look at your older notes). Activation of the Survival Factors RTK would create IP3 (a second messenger), through activation of PI3K. The Chemokine/hormone, ect. GPCR activates adenylate cyclase, creating cAMP (second

messenger) and activating PKA, this pathway could also activate PLC, which would release DAG (second messenger). c. In class today you learned that activation of Akt promotes cell survival. In this diagram which type of receptor activates Akt, and what exactly is Akt doing? The Survival Factors RTK activates Akt, which inhibits Bad, and this pathway blocks initiation of apoptosis. 3. (3) The figure below indicates the signal transduction pathways thought to be involved in polycystic kidney disease (PKD). PC1 and PC2 are the genes whose mutant, nonfunctional forms cause PKD. This may be due to decreased influx of Ca2+ through the calcium channel formed by PC1 and PC2.

a. With the decreased [Ca2+] that occurs with PKD, how is the activity of each the following enzymes changed, relative to normal? (highlight the answer for each) i) adenylyl cyclase (AC-VI) increased decreased unaffected ii) phosphodiesterase (PDE) increased decreased unaffected b. PKA (protein kinase A) is shown to have increased activity in PKD. Explain why the above changes in the activity of adenylyl cyclase and phosphodiesterase influence PKA activity. increased AC activity will cause more cAMP production which will increase activation of PKA.

--phosphodiesterase cleaves/inactivates cAMP, so if decreased in activity, then there is more cAMP and increased activation of PKA c. How do you think the Erb8 receptor activation affects proliferation (cell division) of kidney cells? Increases proliferation because it activates Ras and the MAP kinase pathway...