Regulating the Regulator: Phosphorylation of PKC ? in T Cells.

Protein kinase C ? (PKC ?) is a serine/threonine kinase that is now firmly established as a central component in T cell activation, proliferation, differentiation, and apoptosis (Hayashi and Altman, 2007). Since it was first discovered that PKC ? re-localizes to the immunological synapse (IS) in conventional effector T cells following T cell stimulation, many roles have now been defined for this kinase in these cells such as (a) activation of NF-?B, AP-1, and NFAT transcription factors that control the synthesis of pro-inflammatory cytokines and the anti-apoptotic molecule Bcl-xL (Hayashi and Altman, 2007), (b) regulation of IS dynamics (Sims et al., 2007), (c) up-regulation and clustering of the integrin LFA-1 on the T cell surface (Tan et al., 2006; Letschka et al., 2008) ? thus facilitating stable adhesion between T cells and antigen-presenting cells (APC) and/or migration into inflamed tissues, (d) re-orientation of the microtubule-organizing center toward the APC (Quann et al., 2011), and (e) fine tuning of T cell activation by regulating the intracellular localization, degradation, and internalization of key signaling molecules (Nika et al., 2006; von Essen et al., 2006; Gruber et al., 2009). A new function for PKC ? has also recently been revealed with the finding that this kinase regulates an inducible gene expression program in T cells by associating with chromatin in the nucleus (Sutcliffe et al., 2011)