Find PKA Products Interaction Network for PKA PKA Details

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Synonyms: A-Kinase, cAMP-dependent protein kinase, Pka, Pka protein, Protein kinase A

Activation of PKA through GPCR

Protein kinase A (PKA) is a family of cAMP-dependent protein kinase isozymes that phosphorylate cellular proteins including: Rap-1 (involved with regulation of the Ras/Raf/MEK/ERK pathway at the level of MEK), CREB (cAMP Response Element-Binding protein), RelA (p65) (a subunit of NFkappaB heterodimers), and L-type calcium channels. CAMP (cyclic-AMP) is an important second messenger that is generated from ATP by the actions of adenylate (adenylyl) cyclases (AC). Cells can regulate levels of cAMP induced by external signals through the activation of specific G-protein coupled receptors (GPCRs). GPCRs are receptors linked to heterotrimeric G-proteins composed of (1:1:1) ratios of isoforms of alpha, beta and gamma subunits. The subunits of G-proteins interact with and regulate the activities of various effector molecules such as adenylate cyclase(s). Specificity for activation of adenylate cyclase(s) begins with the specific GPCR receptor. The signal is further refined by the specific isoform composition of the receptor associated trimeric G-protein and the specific iso- form or type of the targeted adenylate cyclase. A variety of AC isozymes exist. Finally kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity.

Adenylate (adenylyl) cyclase(s) are regulated, in part, by the balance of their exposure to specific isoforms of heterotrimeric G-protein alpha subunits; alphaGs (Gα-s) is stimulatory and alphaGi (Gα-i) is inhibitory. AC activity is also regulated by the action of phosphodiesterases that hydrolyze cAMP to AMP and phosphatases that dephosphorylated the phosphorylated PKA substrates.