Epidermal growth factor (EGF) binds to its receptor and activates RAS–MAP kinase signalling. Which step converts inactive RAS-GDP to active RAS-GTP?
- A SOS (son-of-sevenless), a GEF, catalyses GDP/GTP exchange on RAS ✓
- B GTPase-activating protein (GAP) stimulates GTP hydrolysis
- C PKA phosphorylates RAS directly, activating it
- D Phospholipase C cleaves PIP2 to release DAG, which activates RAS
Explanation
After EGF binds, the receptor tyrosine kinase dimerises and autophosphorylates, recruiting adaptor proteins GRB2 and SOS. SOS is a guanine nucleotide exchange factor (GEF) that catalyses the replacement of GDP with GTP on RAS, activating it. GAP (GTPase-activating protein) does the opposite — it accelerates intrinsic GTPase activity to inactivate RAS. Oncogenic RAS mutations impair GTPase activity, trapping RAS in the active GTP-bound form.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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