PKCS

Protein kinase C (PKC) refers to a family of serine/threonine kinases activated by diacylglycerol (DAG) and, for most isozymes, calcium. PKCs phosphorylate diverse substrates and regulate growth, differentiation, metabolism, and apoptosis. The family is divided into three subfamilies: classical PKCs requiring DAG and calcium; novel PKCs requiring DAG but calcium-independent; and atypical PKCs functioning without DAG or calcium. Representative members include classical PKCs α, β, γ; novel PKCs δ, ε, η, θ; and atypical PKCs ζ and ι/λ.

Activation occurs when receptors stimulate phospholipase C to produce DAG and, for classical PKCs, calcium. DAG recruits PKCs to membranes by binding the C1 regulatory domain. Calcium enhances membrane association for classical PKCs via a C2-like domain. Novel PKCs depend on DAG but not calcium; atypical PKCs are regulated by phosphorylation and by interactions with scaffolding proteins and RACKs (receptors for activated C kinase).

PKCs share a conserved C-terminal catalytic kinase domain and an N-terminal regulatory region with a C1 domain that binds DAG; classical PKCs also have a C2-like domain that binds calcium. Activation involves phosphorylation to a mature form, followed by translocation to membranes and substrate phosphorylation. Localization is influenced by anchoring proteins that act as PKC receptors.

PKCs regulate diverse cellular outcomes, including proliferation, differentiation, survival, metabolism, and immune responses. They participate in neuronal signaling, insulin signaling, and platelet function. Dysregulated PKC signaling is linked to cancer, diabetes, neurodegeneration, and inflammatory diseases. PKCs remain targets for therapeutic modulation, with research focusing on isoform-selective inhibitors or activators.