The protein kinase C (PKC) family is represented in all eukaryotes and in Homo sapiens comprises the related PKCα through PKCι gene products (Dempsey et al., 2000). The kinase domains are closely related, as illustrated in the dendrogram, and form part of the AGC kinase superfamily. For clarity, the PKC-related kinases (PRK/PKN) are not included here; similarly excluded is the PKD/PKCµ family, members of which have distinct kinase domains but some related regulatory properties. The three PKC subgroups shown are structurally and functionally distinguished. The conventional, cPKC, isoforms (PKCα, PKCβ and PKCγ) are diacylglycerol (DAG) sensitive and Ca2+ responsive (responding through an archetypal C2 domain). The novel, nPΚC, isoforms (PΚCδ, PΚCε, PΚCη and PΚCθ) are DAG sensitive but Ca2+ insensitive; their C2-related domains do not retain Ca2+-coordinating residues. The atypical, aPKC, isoforms (PKCζ and PKCι/λ) have altered C1 domains and are not DAG sensitive; regulation occurs in part through the N-terminal PB1 domain. Structures for C1 domains and C2 domains have been determined (examples are illustrated for PKCδ), and kinase domain models based on the highly related PKA have been built (that for PKCα is shown here).

Genetic studies in the mouse indicate that particular PKC isoforms are essential in a number of specific contexts, some of which are highlighted here (Abeliovich et al., 1993; Leitges et al., 1996; Hodge et al., 1999; Castrillo et al., 2001; Leitges et al., 2001; Martin et al., 2002; Mecklenbrauker et al., 2002; Miyamoto et al., 2002). However, this is a very much narrower phenotypic profile than is reflected in the rather broad pattern of expression for most of these proteins. Thus it is likely that some functional redundancy exists.