Practice Test 2

Cells express a receptor tyrosine kinase (RTK) that dimerizes upon ligand binding. Dimerization leads to cross-phosphorylation of tyrosines on the cytosolic tails, creating docking sites for adaptor protein A. A recruits and activates Ras by promoting GDP-to-GTP exchange. Ras-GTP activates kinase K1, which activates kinase K2, which activates kinase K3. K3 phosphorylates a cytosolic target protein T, increasing T activity within seconds. In vitro, adding a tyrosine phosphatase that removes phosphates from the RTK tails eliminates Ras-GTP formation despite ligand presence. Which explanation is best supported by these results?

In adipocytes, hormone H binds GPCR R and activates G\alpha$_s$, increasing cAMP and activating PKA. PKA phosphorylates enzyme L, increasing lipolysis. A separate protein, arrestin, binds phosphorylated R and prevents further G protein activation while promoting receptor internalization. In cells lacking arrestin, cAMP remains elevated longer after H addition. Which change would most likely restore normal timing of cAMP decline in arrestin-deficient cells?