TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 INDUCED BY CROSS-LINKING OF THE HIGH-AFFINITY OR LOW-AFFINITY FC RECEPTOR FOR IGG IN U937 CELLS
TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 INDUCED BY CROSS-LINKING OF THE HIGH-AFFINITY OR LOW-AFFINITY FC RECEPTOR FOR IGG IN U937 CELLS
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DOI：
10.1073/pnas.89.8.3659
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发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
RHEE, SG
中科院分区：
文献类型：
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作者：
LIAO, F;SHIN, HS;RHEE, SG
人单核细胞系U937具有两类IgG Fc受体（Fc-γ-R），高亲和力72-kDa Fc-γ-R（Fc-γ-RI）和低亲和力40-kDa Fc-γ-R（Fc-γ-RII）。在U937细胞中，任一类Fc-γ-R的交联均导致细胞内游离Ca 2+浓度的增加。在U937细胞中Fc-γ-Rs交联后，观察到肌醇1，4，5-三磷酸（Ins-1，4，5-P3）和衍生自Ins-1，4，5-P3的几种其他肌醇磷酸的浓度迅速上升。该结果表明，由磷脂酶C（PLC）的作用产生的Ins-1，4，5-P3充当第二信使，Fc-γ-Rs通过该第二信使在U937细胞中动员细胞内Ca 2+。研究了Fc-γ-Rs的交联触发PLC活化的机制。Fc-γ-RI或Fc-γ-RII的交联导致PLC-γ-1在酪氨酸残基上的快速和瞬时磷酸化。先前已经表明，PLC-γ-1在酪氨酸残基上的磷酸化激活其在细胞中的酶活性。预先将U937细胞与蛋白酪氨酸激酶抑制剂除莠霉素A一起温育，防止了由Fc-γ-Rs的交联诱导的PLC-γ-1的酪氨酸磷酸化和磷脂酰肌醇4，5-二磷酸的水解。因此，Fc-γ-RI和Fc-γ-RII似乎在功能上与非受体酪氨酸激酶偶联，所述非受体酪氨酸激酶在受体交联后磷酸化PLC-γ-1，从而引起PLC-γ-1的活化。
The human monocytic cell line U937 possesses two classes of the IgG Fc receptor (Fc-gamma-R), a high-affinity 72-kDa Fc-gamma-R (Fc-gamma-RI) and a low-affinity 40-kDa Fc-gamma-R (Fc-gamma-RII). Cross-linking of either class of Fc-gamma-R in U937 cells elicits an increase in the concentration of free intracellular Ca2+. A rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed after cross-linking of Fc-gamma-Rs in U937 cells. This result suggests that Ins-1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second messenger by which Fc-gamma-Rs mobilize intracellular Ca2+ in U937 cells. The mechanism by which the cross-linking of Fc-gamma-Rs triggers activation of PLC was studied. Cross-linking of Fc-gamma-RI or Fc-gamma-RII resulted in a rapid and transient phosphorylation of PLC-gamma-1 on tyrosine residues. It has previously been shown that phosphorylation of PLC-gamma-1 on tyrosine residues activates its enzymatic activity in cells. prior incubation of U937 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma-1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by the cross-linking of Fc-gamma-Rs. Thus, Fc-gamma-RI and Fc-gamma-RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma-1 after receptor cross-linking, thereby causing activation of PLC-gamma-1.