Aberrant signaling through the EGF receptor signal transduction pathway drives many forms of breast cancer, while misregulation of PI3K drives many prostate cancers. PI3K is one of MANY downstream effectors of EGF receptor signaling, and there are several known activating mutations of PI3K. Would a small molecule that targets PI3K be an effective treatment for a breast cancer that is driven by aberrant signaling through the EGF receptor? Briefly explain your choice. (THIS CAN BE DONE IN LESS THAN TWO SENTENCES, AND MINIMALLY IN ABOUT EIGHT WORDS.)

The egfr kinase independent transactivation of the ras pathway does require egfr. Explain this apparent contradiction.

Binding of TGF-β to its receptors can elicit a variety of responses in different cell types. For example, TGF-β induces plasminogen activator inhibitor 1 in epithelial cells and specific immunoglobulins in B cells. In both cell types, Smad3 is activated. Given the conservation of the signaling pathway, what accounts for the diversity of the response to TGF-β in various cell types?

Draw a cell signaling pathway following EGFR activation in host cells with the possible downstream activities. The new covid-19 strain acts on other cells in the body such as the lungs and kidney via ACE2. (we will say that EGFR is a receptor for the new variant).

TNF-alpha treatment of prostate carcinoma, LNCAP cells decreases cell survival as shown in the graph below. Which of the following would you observe in these cells treated with TNF- alpha? Select all that apply TNF-a 120 100 80 - 60- 40- 20 - 24 72 (hrs) + Control - TNF-a 10ng + TNF-a 100 ng O Activation of extrinsic pathway of apoptosis O Activation of intrinsic pathway of apoptosis Activation of executioner caspases Recruitment of adapter protein FADD to the TNF-alpha receptor LNCAP cell viability (% of control)

What do the cytoplasmic domain of a G protein-coupled receptor and the adaptor protein in the RTK pathway have in common?

Steroid hormones are required by the body at puberty and into adolescence to regulate growth and cell division at more rapid pace than in later life.  This regulation occurs via their interaction with cellular receptors and the signaling cascades/pathways that follow.  Describe for me the difference between the two major classes of steroids, anabolic and catabolic steroids.  What might you expect the result of signaling cascades to be in cells receiving either anabolic or catabolic “signals”? (B) At some point in late adolescence, steroid production decreases by almost 100 fold, as we transition into “adulthood”.  Why might we wish to stop these signals from constantly being in our blood stream, (like, Say, between 17-24 years of age)?  What result might these steroids have on cancer cells where abhorrent signaling is already causing an increased rate of cell division/growth? Could steroid use result in Cancer?

Suppose that you measured binding to the isolated EGF receptor of EGFat various concentrations. Would you expect the binding curve to be hyperbolic? Explain your answer.

You 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?

Give an overview of the pathway and what it does, and explain the nature of the TNF ligand and the receptor for that ligand. Make sure to include an explanation of the proteolytic and phosphorylation cascades.