The protein kinase C (PKC; EC 2.7.11.13) family represents a large group of phospholipid dependent enzymes catalyzing the covalent transfer of phosphate from ATP to serine and threonine residues of proteins, mediating signal transduction for cell proliferation, differentiation, apoptosis and angiogenesis. The PKC family consists of at least twelve members, divided into three subgroups: the classical PKCs (cPKCs: PKCα, PKCβI, PKCβII, and PKCγ), which are Ca2+ dependent and activated by both phosphotidylserine (PS) and diacylgylcerol (DAG); novel PKCs (nPKCs: PKCδ, PKCε, PKCη, and PKCθ), which are Ca2+ independent and regulated by DAG and PS; and atypical PKCs (aPKCs: PKCζ, PKCλ), which are Ca2+ independent and do not require DAG for activation, although PS can regulate their activity. Many of these kinases show overlapping substrate specificities in vitro. Consistent with their different biological functions, PKC isoforms differ in their structure, tissue distribution, subcellular localization, mode of activation and substrate specificity. Early observations that PKC isozymes are activated by tumor-promoting phorbol esters suggested a key role for PKC in tumor promotion and progression leading to PKC being considered as a target for cancer therapy