Protein kinase C family (PKC)

The Protein Kinase C (PKC) family consists of a diverse group of serine/threonine kinases that function as key nodes in intracellular signaling pathways (UniProt, 2023). These enzymes are traditionally classified into three subfamilies based on their second messenger requirements: conventional PKCs (alpha, beta, gamma) which require calcium and diacylglycerol (DAG); novel PKCs (delta, epsilon, eta, theta) which require DAG but are calcium-independent; and atypical PKCs (zeta, iota/lambda) which require neither (NIH, 2022). PKCs regulate a vast array of cellular processes, including growth, differentiation, and apoptosis, by phosphorylating downstream targets like MARCKS (PubMed, 2021). In clinical contexts, PKC dysregulation is heavily implicated in cancer, where specific isoforms can act as either oncoproteins or tumor suppressors, and in diabetic complications such as retinopathy and nephropathy (StatPearls, 2023). While therapeutic targeting of PKCs has been explored for decades with drugs like Midostaurin and Ruboxistaurin, the high structural homology between isoforms often results in poor selectivity, leading to significant safety concerns and therapeutic challenges in clinical trials (Nature Reviews Drug Discovery, 2020). The term "Other PKC isoforms" is considered an incorrect or vague target designation as it does not specify which of the distinct family members is being addressed.

Other names

Other PKC isoformsPKC familySerine/threonine-protein kinase CPKCs

Inhibition of the catalytic kinase domain through ATP-competitive binding or modulation of the regulatory domains (C1 and C2) to prevent membrane translocation and subsequent activation.