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Sci. STKE, 28 September 2004
Vol. 2004, Issue 252, p. tw345
[DOI: 10.1126/stke.2522004tw345]

EDITORS' CHOICE

SURVIVAL SIGNALS Nuclear PKC{delta} Is Deadly

Previously, this group reported that mice deficient for protein kinase C{delta} (PKC{delta}) exhibit a lupus-like autoimmune disease, which is typically caused by proliferation of autoreactive B cells. Overexpression of BAFF (B cell-activating factor belonging to the tumor necrosis factor family) also causes a similar phenotype in mice. Now Mecklenbräuker et al. show that PKC{delta} deficiency results in mice that do not show decreased B cell numbers or maturation in response to injection of a BAFF decoy. Furthermore, PKC{delta}-deficient mice that were also expressing a signaling-deficient form of the BAFF receptor did not show reduced sizes in lymphoid organs or fewer peripheral B cells that are typical of mice in which BAFF signaling is blocked. Isolated PKC{delta}–/– B cells showed increased life-span in culture compared to that of wild-type B cells, and this effect was not due to increased production of the survival factor interleukin 6 (IL-6). Furthermore, PKC{delta} deficiency did not rescue B cells from apoptosis caused by Btk deficiency (Btk stands for Bruton's tyrosine kinase and is part of an antiapoptotic signaling cascade). Isolated splenic B cells from wild-type mice were susceptible to cell death and exhibited an increase in nuclear PKC{delta} 24 hours after exposure to serum-containing medium. Exposure of isolated B cells to BAFF prevented nuclear accumulation of PKC{delta}, and overexpression of PKC resulted in an increase in the abundance of phosphorylated histone 2B at serine 14 (S14-H2B), a phosphorylation event known to be associated with cell death. PKC{delta}-deficient B cells exhibited decreased abundance of S14-H2b compared with wild-type B cells. Thus, BAFF can mediate cell survival by inhibiting nuclear PKC{delta} activity.

I. Mecklenbräuker, S. L. Kalled, M. Leitges, F. Mackay, A. Tarakhovsky, Regulation of B-cell survival by BAFF-dependent PKC{delta}-mediated nuclear signalling. Nature 431, 456-461 (2004). [Online Journal]

Citation: Nuclear PKC{delta} Is Deadly. Sci. STKE 2004, tw345 (2004).


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