Sci. STKE, 7 October 2003
IMMUNOLOGY A Lipase-Free PLC-Like Protein
Phospholipase C (PLC) cleaves phosphatidylinositol 4,5-bisphosphate to form the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. Recently, PLC-L2, a PLC-like protein that lacks lipase activity, has been identified in skeletal muscle, as well as in B and T lymphocytes. Takenaka et al. generated PLC-2-deficient mice to investigate the possible role of PLC-2 signaling in B lymphocytes. PLC-L2-deficient mature B cells showed an enhanced proliferative response and increased expression of the activation marker CD69 after B cell receptor (BCR) stimulation in vitro, and mice displayed increased production of immunoglobulin M (IgM), IgG1, and IgG3 in response to antigen treatment in vivo. The authors used fura-2 imaging to show that Ca2+ influx after BCR stimulation was enhanced in PLC-2-deficient cells; moreover, translocation of nuclear factor of activated T cells (which is regulated by calcineurin, which is itself calcium-dependent) was enhanced. Finally, PLC-2-deficient cells showed increased phosphorylation of extracellular signal-regulated kinase and activation of the transcription factor AP-1 after BCR stimulation, which indicated that signaling through the mitogen-associated protein kinase pathway was enhanced. Thus, B cells from PLC-2-deficient mice showed a hyperreactive response to BCR stimulation; the authors suggest that PLC-2 acts as an inhibitory regulator of BCR signaling and of the B cell immune response.
K. Takenaka, K. Fukami, M. Otsuki, Y. Nakamura, Y. Kataoka, M. Wada, K. Tsuji, S.-I. Nishikawa, N. Yoshida, T. Takenawa, Role of phospholipase C-L2, a novel phospholipase-C-like protein that lacks lipase activity in B-cell receptor signaling. Mol. Cell. Biol. 23, 7329-7338 (2003). [Abstract] [Full Text]
Citation: A Lipase-Free PLC-Like Protein. Sci. STKE 2003, tw393 (2003).
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