Takata M, Homma Y, Kurosaki T
Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, New York 10965, USA.
J Exp Med. 1995 Oct 1;182(4):907-14. doi: 10.1084/jem.182.4.907.
Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-gamma 2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2 through Syk is required for sIgM-induced apoptosis.
表面免疫球蛋白M(sIgM)刺激可诱导多种细胞底物的酪氨酸磷酸化,包括参与磷脂酰肌醇途径激活的磷脂酶C(PLC)-γ2。当通过sIgM激活时,DT40 B细胞会经历凋亡性细胞死亡,这一现象与自身反应性B细胞的清除有关。为了研究PLC-γ2在sIgM信号传导中的作用,我们构建了PLC-γ2缺陷的DT40细胞。在PLC-γ2缺陷细胞上对sIgM进行交联既不会引起肌醇1,4,5-三磷酸的产生,也不会引起钙动员。在PLC-γ2或Syk缺陷的DT40细胞中,凋亡的诱导被阻断,但在Lyn缺陷细胞中仍可观察到凋亡。PLC-γ2的Src同源2结构域对其激活和sIgM诱导的凋亡都至关重要。由于PLC-γ2的酪氨酸磷酸化是由Syk介导的,这些结果表明通过Syk激活PLC-γ2是sIgM诱导凋亡所必需的。