cPKC

cPKC, or classical protein kinase C, refers to a subset of the PKC family that phosphorylates serine and threonine residues in response to calcium and diacylglycerol (DAG). In humans, the classical isoforms are PKC alpha (PRKCA), PKC beta I (PRKCB1), PKC beta II (PRKCB2), and PKC gamma (PRKCG). These enzymes are distinguished from the novel PKCs, which are DAG-activated but calcium-independent, and from the atypical PKCs, which require neither DAG nor Ca2+ for activation.

Structurally, cPKCs have a regulatory N-terminal region containing a C1 domain that binds DAG and phorbol esters, a C2-like domain that binds Ca2+ in conventional PKCs, and a C-terminal kinase catalytic domain. In the resting state, a pseudosubstrate sequence in the regulatory region autoinhibits the catalytic domain. Elevations in intracellular Ca2+ and production of DAG recruit cPKCs to membranes, relieve autoinhibition, and enable substrate phosphorylation.

Activation typically follows phospholipase C–coupled receptor signaling or receptor tyrosine kinase pathways, where phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved to generate IP3 (raising Ca2+) and DAG. DAG and Ca2+ together promote translocation to membranes and activation. Phorbol esters can mimic DAG and trigger prolonged cPKC activation, though prolonged exposure may lead to downregulation.

cPKCs participate in diverse physiological processes, including regulation of cell growth, differentiation, survival, and migration, as well as roles in immune signaling and neuronal function. Deregulation of cPKC activity has been associated with various diseases, including cancer and cardiovascular disorders.