Which of the following best predicts the effect of inhibiting cyclic AMP phosphodiesterase in a muscle cell stimulated by epinephrine?

1. The proliferation of thyroid cells is stimulated by hormones that activate a receptor coupled to Gs. How would inhibitors of cAMP phosphodiesterase affect the proliferation of these cells?

Inhibition of cAMP phosphodiesterase would result in elevated levels of cAMP, which would stimulate cell proliferation.

2. The epinephrine receptor is coupled to Gs, whereas the acetylcholine receptor (on heart muscle cells) is coupled to Gi. Suppose you were to construct a recombinant molecule containing the extracellular sequences of the epinephrine receptor joined to the cytosolic sequences of the acetylcholine receptor. What effect would epinephrine have on cAMP levels in cells expressing such a recombinant receptor? What would be the effect of acetylcholine?

The recombinant molecule would function as an epinephrine receptor coupled to Gi. Epinephrine would therefore inhibit adenylyl cyclase, lowering intracellular cAMP levels. Acetylcholine would have no effect, since it would not bind to the recombinant receptor.

3. Platelet-derived growth factor (PDGF) is a dimer of two polypeptide chains. What would be the predicted effect of PDGF monomers on signaling from the PDGF receptor?

PDGF monomers would not induce receptor dimerization. Since this is the first critical step in signaling from receptor protein-tyrosine kinases, they would be unable to stimulate the PDGF receptor.

4. How would overexpression of protein phosphatase 1 affect the induction of cAMP-inducible genes in response to hormone stimulation of appropriate target cells? Would protein phosphatase 1 affect the function of cAMP-gated ion channels involved in odorant reception?

Protein phosphatase 1 dephosphorylates serine residues that are phosphorylated by protein kinase A. Cyclic AMP-inducible genes are activated by CREB, which is phosphorylated by protein kinase A, so overexpression of protein phosphatase 1 would inhibit their induction. However, protein phosphatase 1 would not affect the activity of cAMP-gated ligand channels, since these channels are opened directly by cAMP binding rather than by protein phosphorylation.

5. Protein kinase C-α (PKC-α) and protein kinase C-ε (PKC-ε) are two different members of the protein kinase C family, which differ in their regulation. PKC-α requires both Ca2+ and diacylglycerol for activation, whereas PKC-ε requires only diacylglycerol. How would hydrolysis of the phospholipids PIP2 and phosphatidylcholine by phospholipase C affect the activities of these different PKC family members?

Hydrolysis of PIP2 by phospholipase C yields both diacylglycerol and IP3, which signals the release of Ca2+ from the endoplasmic reticulum. PIP2 hydrolysis can therefore activate both PKC-α and PKC-ε. Hydrolysis of phosphatidylcholine yields diacylglycerol but not IP3; consequently, phosphatidylcholine hydrolysis is sufficient to activate PKC-ε but not PKC-α.

6. Dominant negative mutants of both Ras and Raf block growth factor-stimulated cell proliferation. The inhibitory effects of dominant negative Ras are overcome by expression of activated Raf. Would you expect activated Ras similarly to overcome the inhibitory effects of dominant negative Raf? How about activated MEK?

Raf acts downstream of Ras in the MAP kinase pathway. Activated Raf can therefore bypass the effects of dominant negative Ras, but activated Ras cannot overcome the inhibitory effects of dominant negative Raf. MEK acts downstream of Raf, so activated MEK can overcome the effects of dominant negative Ras or Raf.

Which of the following statements best describes the role of adenylyl cyclase in the epinephrine signaling pathway quizlet?

Which of the following statements best describes the role of cyclic AMP in the signal transduction pathway quizlet?

What is the role of adenylyl cyclase in the epinephrine signaling pathway?

Which of the following effects on the coagulation cascade is most likely to result from inhibiting thrombin activity with argatroban?