A patient with McCune-Albright syndrome has constitutively active Gs-alpha protein due to a somatic mutation at Arg201. The DIRECT biochemical consequence in the affected cells is:

• A Permanently elevated IP3 and DAG due to constitutive activation of phospholipase C
• B Constitutive activation of tyrosine kinase receptor downstream signalling via RAS-MAPK
• C Permanently elevated intracellular cAMP due to constitutive activation of adenylyl cyclase ✓
• D Loss of receptor desensitisation due to inability of GRK2 to phosphorylate the receptor

Explanation

Gs-alpha normally hydrolyses its bound GTP to GDP, terminating signalling; the Arg201 mutation impairs intrinsic GTPase activity so Gs-alpha remains in its GTP-bound active form, constitutively stimulating adenylyl cyclase and keeping cAMP permanently elevated. This activates PKA constitutively in multiple tissues, causing cafe-au-lait spots, fibrous dysplasia, and precocious puberty. PLC/IP3 signalling involves Gq, not Gs. RAS-MAPK is downstream of receptor tyrosine kinases.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.