Glucagon mobilizes hepatic glucose during fasting. The post-receptor signaling sequence that couples the glucagon receptor to glycogen breakdown is:

• A Gq protein, phospholipase C, IP3-mediated calcium release, calmodulin activation
• B Gs protein, increased cAMP, PKA activation, phosphorylation of phosphorylase kinase ✓
• C Receptor tyrosine kinase, IRS phosphorylation, PI3 kinase, GLUT2 insertion
• D JAK2 activation, STAT5 dimerization, transcription of glycogen phosphorylase

Explanation

The glucagon receptor is a classic Gs-coupled GPCR. Raised cAMP activates protein kinase B, which phosphorylates and activates phosphorylase kinase, converting glycogen phosphorylase b to active phosphorylase a and driving glycogenolysis. PKA also phosphorylates CREB to induce gluconeogenic enzymes such as PEPCK. The Gq-IP3 cascade applies to receptors like alpha-1 adrenergic and angiotensin II, and the tyrosine kinase pathway belongs to insulin.

Reference: Lippincott Illustrated Reviews: Biochemistry, 8th ed.

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