The PKC gene module: molecular biosystematics to resolve its T cell functions

The distinct protein kinase C (PKC) multigene family (PKC gene module) is known to be the 'classic' intracellular receptor for mitogenic phorbol esters, and it is widely accepted in the scientific community that the 'PKC effect' is essential in activation, differentiation, adhesion and motility, as well as in cellular survival, of T cells. Nevertheless, the first concepts about PKC isotype heterogeneity of cellular localization and function emerged only recently, when the PKC-theta pathways were mapped to critical signaling networks that control T cell receptor (TCR)/CD3-dependent interleukin (IL)-2 production and proliferation in T lymphocytes. This review summarizes the current knowledge about T cell expressed PKC gene products, their known and/or suspected regulation and cellular effector pathways, as well as physiological functions in T lymphocytes (as determined by molecular cell biology and ongoing mouse genetic studies). Given PKCs integral role in T cell function but today's very fragmentary molecular understanding of directly PKC-mediated effector functions in transmembrane signaling, a 'molecular biosystematics' approach is suggested to resolve the isotype-selective functions of this PKC gene family. Such an approach has to be based not only on genomic/cytogenetic analysis to establish its genetic relationships but also on biochemical/cell biology and genetic studies to resolve its functional diversity and, ultimately, nonredundant roles in real T cell physiology.