Protein kinase C (conventional and novel isoforms) (PKC)

Protein kinase C (PKC) represents a family of serine/threonine kinases essential for transducing signals that regulate a wide array of cellular processes, including growth, differentiation, and programmed cell death [StatPearls, 2023]. This target group specifically encompasses the conventional isoforms (alpha, beta, and gamma), which are activated by calcium and diacylglycerol (DAG), and the novel isoforms (delta, epsilon, eta, and theta), which are DAG-dependent but calcium-insensitive [NIH, 2022]. In various pathologies, these kinases are often dysregulated; for example, PKC-alpha and PKC-epsilon are frequently overexpressed in cancers to promote survival, while PKC-beta is a key mediator of diabetic microvascular complications [MDPI Cancers, 2022]. Conversely, certain isoforms like PKC-delta can exhibit tumor-suppressive properties by inducing apoptosis under specific conditions, highlighting the complex and often opposing roles of different family members [NIH, 2017]. Pharmacological intervention has historically been difficult due to the high structural conservation between isoforms, but modern efforts focus on selective inhibitors like midostaurin and enzastaurin to treat malignancies and inflammatory conditions [Frontiers in Pharmacology, 2021]. Additionally, novel approaches like peptide inhibitors that block isoform-specific translocation to the cell membrane are being explored to overcome the limitations of ATP-competitive inhibitors [MDPI, 2022]. Overall, the conventional and novel PKC isoforms remain significant therapeutic targets across oncology, cardiology, and immunology [Frontiers in Oncology, 2021].

Other names

PKCcPKCnPKCConventional PKCNovel PKCProtein kinase C alphaProtein kinase C betaProtein kinase C gammaProtein kinase C deltaProtein kinase C epsilonProtein kinase C etaProtein kinase C thetaPRKCAPRKCBPRKCGPRKCDPRKCEPRKCHPRKCQ

Drugs targeting conventional and novel PKC isoforms primarily act through ATP-competitive inhibition of the catalytic domain, modulation of the C1 regulatory domain (mimicking or antagonizing diacylglycerol), or by interfering with isoform-specific translocation to the cell membrane via RACK (Receptor for Activated C-Kinase) binding inhibition [NIH, 2022; MDPI, 2022].