Protein kinase C zeta and Protein kinase C iota (aPKC)

Atypical protein kinase C (aPKC) isoforms, specifically Protein kinase C zeta (PKCζ) and Protein kinase C iota (PKCι, with PKCλ being the mouse ortholog), are serine/threonine kinases that function as critical signaling hubs in various cellular processes. Unlike other PKC subfamilies, aPKCs are independent of calcium and diacylglycerol, instead being regulated by protein-protein interactions and phosphoinositides. They play a central role in establishing cell polarity through the Par complex (comprising Par3, Par6, and aPKC) and are involved in insulin-stimulated glucose transport, NF-κB activation, and cell survival pathways. In oncology, PKCι is frequently characterized as an oncogene, particularly in lung and pancreatic cancers, while PKCζ can act as either a tumor promoter or suppressor depending on the tissue context. Therapeutic strategies include small molecule inhibitors targeting the catalytic domain or the PB1 protein-interaction domain, with agents like aurothiomalate having reached clinical evaluation for cancer treatment.

Other names

PKCζPKCιPKCλPRKCZPRKCIAtypical protein kinase CPKC-zetaPKC-iotaPKC-lambdanPKC-zetaPKC2

Inhibition of kinase activity through ATP-competitive binding or disruption of protein-protein interactions via the PB1 domain.