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Name _Key_____________________________________ 1. Using what you know about cell signaling and regulation, why do you think most (if not all) drugs have side effects? (Below is an example of a signaling network in a pancreatic β-cell). B Insulin secretion and biosynthesis Prevent cell death A improve function and survival under stress inducing β-cell proliferation 2. Using the figure above: a. What is the effect of a drug which inhibits cyclin D1 (labeled as A)? Inhibiting cyclin D1 will prevent the induction of β-cell proliferation b. What is the effect of a drug which activates adenylyl cyclase (labeled as B)? A drug which activates adenylyl cyclase will have many effects. It will activate insulin secretion and biosynthesis. It will improve function and survival under stress. It will induce β-cell proliferation. c. What does this tell you about how to choose a drug target for a specific pathway? A target at the top of a pathway (like adenylyl cyclase) will have more unintended consequences because it feeds into many other pathways. To limit affecting other pathways, you should choose a drug target near the bottom of a pathway as close to the desired outcome as possible. 3. Using the diagram above, fill out the table to describe this regulatory cascade. Step 1 effector molecule Target molecule Method of regulation epinephrine β-adrenergic receptor conformational change 2 β-adrenergic receptor G-protein Conformational change 3 G-protein adenylate cyclase Protein interactions 4 adenylate cyclase ATP/Cyclic AMP 5 Cyclic AMP protein kinase A Production of secondary messenger conformational change 6 Protein Kinase A a. phosphorylase a. phosphorylation kinase b. glycogen b. phosphorylation synthase phosphorylase phosphorylase a phosphorylation kinase 7