Epidermal growth factor (EGF) binding to its receptor leads to activation of the MAP kinase cascade. The adaptor protein Grb2 couples the activated receptor to the guanine nucleotide exchange factor SOS. SOS then activates RAS by promoting the exchange of GDP for GTP. Which of the following proteins enhances the intrinsic GTPase activity of RAS to terminate signaling?

• A Growth factor receptor-bound protein 2 (Grb2)
• B Son of sevenless (SOS)
• C Guanine nucleotide exchange factor (GEF)
• D GTPase-activating protein (GAP) ✓

Explanation

RAS is a small GTPase that is active when GTP-bound and inactive when GDP-bound. GAPs (GTPase-activating proteins) bind RAS and dramatically accelerate its intrinsic GTPase activity, hydrolyzing GTP to GDP and switching RAS off. GEFs like SOS promote GDP release and GTP loading, activating RAS. Grb2 is an adaptor linking the receptor to SOS. Loss of GAP function (e.g., neurofibromin mutations) leads to prolonged RAS signaling.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.