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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