Protein kinase A (PKA), also known as cAMP-dependent protein kinase, is a serine/threonine-specific kinase that exists in the resting state as an inactive tetramer of two regulatory (R) and two catalytic (C) subunits. Binding of four cAMP molecules to the regulatory subunits releases the catalytic subunits, which then phosphorylate a broad set of downstream substrates on serine or threonine residues within the consensus motif RRXS/T.
PKA is the principal effector of Gs-coupled receptor signalling. Its substrates include the transcription factor CREB, metabolic enzymes such as phosphorylase kinase and hormone-sensitive lipase, ion channels, and multiple regulatory phosphatases and kinases. A-kinase anchoring proteins (AKAPs) localise PKA to specific subcellular compartments, providing spatial specificity to the response.
PKA activation is the canonical downstream event by which Gs-coupled peptide receptors — GLP-1R and its family — exert their effects at the cellular level.