1. Role of Phospholipase C-L2, a Novel Phospholipase C-Like Protein That Lacks Lipase Activity, in B-Cell Receptor Signaling.
- Author
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Takenaka, Kei, Fukami, Kiyoko, Otsuki, Makiko, Nakamura, Yoshikazu, Kataoka, Yuki, Wada, Mika, Tsuji, Kochichiro, Nishikawa, Shin-Ichi, Yoshida, Nobuaki, and Takenawa, Tadaomi
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PHOSPHOLIPASE C ,PROTEIN kinase C ,CELLULAR signal transduction - Abstract
Phospholipase C (PLC) plays important roles in phosphoinositide turnover by regulating the calciumprotein kinase C signaling pathway. PLC-L2 is a novel PLC-like protein which lacks PLC activity, although it is very homologous with PLC δ. PLC-L2 is expressed in hematopoietic cells, but its physiological roles and intracellular functions in the immune system have not yet been clarified. To elucidate the physiological function of PLC-L2, we generated mice which had a genetic PLC-L2 deficiency. PLC-L2-deficient mice grew with no apparent abnormalities. However, mature B cells from PLC-L2-deficient mice were hyperproliferative in response to B-cell receptor (BCR) cross-linking, although B2 cell development appeared to be normal. Molecular biological analysis revealed that calcium influx and NFATc accumulation in nuclei were increased in PLC-L2-deficient B cells. Extracellular signal-regulated kinase activity was also enhanced in PLC-L2deficient B cells. These mice had a stronger T-cell-independent antigen response. These results indicate that PLC-L2 is a novel negative regulator of BCR signaling and immune responses. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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