A research study demonstrates that a Gs protein-coupled receptor agonist increases cAMP. The elevated cAMP activates PKA, which phosphorylates CREB. What is the direct molecular consequence of CREB phosphorylation at Ser133?

• A CREB recruits CBP/p300 co-activator and drives CRE-containing gene transcription ✓
• B CREB is ubiquitinated and targeted for proteasomal degradation
• C CREB dimerises with NF-κB to activate inflammatory gene promoters
• D CREB is exported from the nucleus to terminate signal transduction

Explanation

PKA phosphorylates CREB (cAMP response element-binding protein) at serine-133, which creates a binding site for the transcriptional co-activator CBP (CREB-binding protein)/p300. CBP/p300 has intrinsic histone acetyltransferase activity, opens chromatin at CRE (cAMP response element) loci, and bridges CREB to the basal transcriptional machinery, activating genes involved in gluconeogenesis (PEPCK), cortisol biosynthesis, memory consolidation, and many others. CREB is not degraded, exported, or partnered with NF-κB in this pathway.

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

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