FcgammaRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization.
FcgammaRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization.
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FcgammaRIIB 介导的 T 细胞受体信号转导抑制涉及含 SH2 的肌醇 5-磷酸酶 (SHIP) 的磷酸化、活化 T 细胞 (LAT) 接头的去磷酸化以及钙动员的抑制。
DOI：
10.1042/0300-5127:0290840
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发表时间：
2001
影响因子：
3.9
通讯作者：
Cambier,JC
中科院分区：
文献类型：
--
作者：
Jensen,WA;Marschner,S;Ott,VL;Cambier,JC
免疫球蛋白G的低亲和力受体FcγRIIB在大多数b细胞和未成熟和活化的成熟t细胞上表达。FcγRIIB与b细胞抗原受体（BCR）共聚集，通过抑制p21ras、磷脂酰肌醇3-激酶（PI3-K）和磷脂酶Cγ (PLCγ)的激活，导致BCR诱导的囊胚发生和细胞增殖的衰减。这些作用至少部分是由含sh2蛋白酪氨酸磷酸酶-1 （SHP-1）和-2 （SHP-2）以及含sh2肌醇5-磷酸酶（SHIP）的募集介导的。在本报告中，我们证明了FcγRIIB与t细胞抗原受体（TCR）共聚集，这可能发生在t细胞识别抗体包被的靶细胞时，导致TCR诱导的活化t细胞连接体（LAT）磷酸化被抑制。当磷酸化时，LAT作为适配器分子并招募PI3-K。此外，我们证明了PI3-K是tcr诱导的Ca2+动员所必需的。总之，这些数据表明，FcγRIIB可能抑制tcr介导的Ca2+动员，部分是通过抑制LAT磷酸化和随后抑制PI3-K活化。在b细胞中也描述了类似的机制，其中FcγRIIB与BCR共聚集通过CD19的去磷酸化导致PI3-K活性的抑制。在这两种细胞类型中，PtdIns(3,4,5) p3的水平可能通过SHIP的酶活性被额外调节。
The low-affinity receptor for immunoglobulin G, FcγRIIB, is expressed on most B-cells and on immature and activated mature T-cells. Co-aggregation of FcγRIIB with the B-cell antigen receptor (BCR) leads to attenuation of BCR-induced blastogenesis and cell proliferation via inhibition of p21ras, phosphatidylinositol 3-kinase (PI3-K) and phospholipase Cγ (PLCγ) activation. These effects are mediated, at least in part, by the recruitment of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and -2 (SHP-2) and SH2-containing inositol 5-phosphatase(SHIP). In this report, we demonstrate that FcγRIIB co-aggregation with the T-cell antigen receptor (TCR), which may occur when T-cells recognize antibody-coated target cells, leads to inhibition of TCR-induced phosphorylation of the linker of activated T-cells (LAT). When phosphorylated, LAT functions as an adapter molecule and recruits PI3-K. Additionally, we demonstrate that PI3-K is required for TCR-induced Ca2+mobilization. Together, these data suggest that FcγRIIB may inhibit TCR-mediated Ca2+mobilization, in part via inhibition of LAT phosphorylation and subsequent inhibition of PI3-K activation. A similar mechanism has been described in B-cells, where FcγRIIB co-aggregation with the BCR leads to inhibition of PI3-K activity via dephosphorylation of CD19. It is likely that, in both cell types, levels of PtdIns(3,4,5)P3are additionally modulated via the enzymic activity of SHIP.