Members of the protein kinase C (PKC) family are expressed in many different cell types, where they are known to regulate a wide variety of cellular processes that impact on cell growth and differentiation, cytoskeletal remodelling and gene expression in the response to diverse stimuli. The broad tissue distribution and redundancy of in vitro function have often hampered the identification of definitive roles for each PKC family member. However, recent in vivo studies of PKC isoenzyme-selective knockout and transgenic mice have highlighted distinct functions of individual PKCs in the immune system. These genetic analyses, along with biochemical studies utilizing PKC isoenzyme-specific cDNA (wild-type, constitutively active and dominant-negative), antisense oligonucleotides (ASO), RNA interference (RNAi), and pharmacological inhibitors, indicate that PKC-regulated signalling pathways play a significant role in many aspects of immune responses, from development, differentiation, activation and survival of lymphocytes to macrophage activation. The importance of PKCs in cellular immune responses suggests that improved understanding of the molecular events that govern their actions could point to new avenues for development of treatments for immune disorders.
Abbreviations used: AP-1, activator protein-1; APC, antigen-presenting cell; BCR, B-cell receptor; Btk, Bruton's tyrosine kinase; CARD, caspase recruitment domain; CARMA1, CARD/membrane-associated guanylate kinase; CAT, catalytic domain of PKC; DAG, diacylglycerol; ERK, extracellular-signal-regulated kinase; ICAM-1, intercellular cell-adhesion molecule 1; IFNγ, interferon-γ; IκB, inhibitory κB; IKK, IκB kinase; IL, interleukin; IS, immunological synapse; JNK, c-Jun N-terminal kinase; LFA-1, lymphocyte-function-associated antigen-1; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; NFAT, nuclear factor of activated T-cells; PKC, protein kinase C; aPKC, atypical PKC; cPKC, conventional PKC; nPKC, novel PKC; RNAi, RNA interference; SFK, Src family protein tyrosine kinase; TCR, T-cell receptor; TNFα, tumour necrosis factor α; WASP, Wiskott–Aldrich syndrome protein; WIP, WASP-interacting protein.