A patient with McCune-Albright syndrome has constitutively active Gs-alpha protein in multiple tissues. Which of the following signal transduction components is DIRECTLY activated by this mutant Gs-alpha?

• A Phospholipase C-beta, increasing IP3 and DAG
• B Receptor tyrosine kinase, activating the RAS-MAPK pathway
• C Adenylyl cyclase, elevating intracellular cAMP ✓
• D Guanylyl cyclase, raising intracellular cGMP

Explanation

Gs-alpha activates adenylyl cyclase (AC), which converts ATP to cAMP. In McCune-Albright syndrome, a somatic gain-of-function mutation in GNAS1 prevents intrinsic GTPase activity of Gs-alpha, keeping it constitutively active and causing persistent cAMP elevation in affected tissues (bone, skin, endocrine glands), leading to precocious puberty, café-au-lait spots, and fibrous dysplasia. Phospholipase C-beta is activated by Gq, not Gs.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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