cPKCs

Conventional protein kinase C (cPKC) refers to a subset of the protein kinase C family that includes PKC alpha, PKC beta (two splice variants, βI and βII), and PKC gamma. These serine/threonine kinases are activated by increases in intracellular calcium and diacylglycerol (DAG), and they require phospholipids for full activation. They are distinct from novel and atypical PKCs in their dependence on Ca2+.

cPKCs share a modular structure: an N-terminal regulatory region containing a C1 domain that binds DAG and phorbol esters, a C2-like calcium-binding domain, and a C-terminal catalytic kinase domain. In the resting state, the regulatory region inhibits the catalytic domain. Elevation of Ca2+ and DAG causes the regulatory regions to bind these ligands, releasing autoinhibition and enabling substrate phosphorylation. Activation is further modulated by phosphorylation at activation sites by upstream kinases such as PDK1 and mTORC2, which prime the enzyme for full activity.

Functionally, cPKCs phosphorylate a range of substrates to influence signaling pathways that govern cell proliferation, differentiation, apoptosis, cytoskeletal dynamics, and gene expression. They are widely expressed with isoform-specific tissue distribution and participate in pathways including MAPK and NF-κB signaling.

Dysregulation of cPKCs has been associated with diseases such as cancer and cardiovascular or neurodegenerative conditions. Therapeutic approaches include isoform-selective inhibitors and modulators, though achieving precise, context-dependent effects remains challenging.