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首页> 外文期刊>Cellular Signalling >Heterologous regulation of chemokine receptor signaling by the lipid phosphatase SHIP in lymphocytes
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Heterologous regulation of chemokine receptor signaling by the lipid phosphatase SHIP in lymphocytes

机译：脂质磷酸酶SHIP对淋巴细胞趋化因子受体信号的异源调节

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The SH2 domain-containing inositol polyphosphate 5-phosphatase (SHIP) is known to play an important role in the negative regulation by Fc gamma RIIB of PI3K-dependent signaling cascades activated by the B cell antigen receptor (BCR) as well as several tyrosine-kinase coupled cytokine receptors. However, to date the role of SHIP in the regulation of PI3K-dependent signals elicited by G-protein-coupled receptors (GPCR) such as chemokine receptors has not been investigated. In this study, we report that ligation of the G-protein-coupled chemokine receptor CXCR4 by SDF-1/CXCL12 has no effect on the tyrosine phosphorylation of SHIP in the murine B cell lymphoma A20. However, co-ligation of the B cell antigen receptor and Fc-yRIIB inhibits the PI3K-dependent phosphorylation of PKB and ERK1/2 in response to CXCL12. We have also utilised a constitutively active membrane-localised SHIP mutant expressed in the Jurkat leukaemic T cell line (which do not normally express SHIP), in order to investigate the effect of this mutant on CXCL12 stimulated PI3K-dependent signaling events. Experiments have revealed that CXCL12-mediated PKB phosphorylation, chemotaxis and lipid accumulation are inhibited in the presence of this SHIP mutant. Thus, it appears that heterologous activation of SHIP by-non-G-protein-coupled receptor-mediated routes can impinge on PI3K-dependent signaling pathways activated by independently ligated G-protein-coupled chemokine receptors. (c) 2004 Elsevier Inc. All rights reserved.
机译：已知含有SH2结构域的肌醇多磷酸5-磷酸酶（SHIP）在FcγRIIB对B细胞抗原受体（BCR）激活的PI3K依赖性信号级联反应以及几种酪氨酸激活的负调控中起着重要作用。激酶偶联的细胞因子受体。然而，迄今为止，尚未研究SHIP在调节由G蛋白偶联受体（GPCR）例如趋化因子受体引起的PI3K依赖性信号中的作用。在这项研究中，我们报告说，SDF-1 / CXCL12与G蛋白偶联趋化因子受体CXCR4的连接对鼠B细胞淋巴瘤A20中SHIP的酪氨酸磷酸化没有影响。但是，B细胞抗原受体和Fc-yRIIB的共连接抑制了响应CXCL12的PKB和ERK1 / 2的PI3K依赖性磷酸化。为了研究该突变体对CXCL12刺激的PI3K依赖性信号传导事件的影响，我们还利用了在Jurkat leukaemic T细胞系中表达的组成性活性膜定位SHIP突变体（通常不表达SHIP）。实验表明，在该SHIP突变体的存在下，CXCL12介导的PKB磷酸化，趋化性和脂质蓄积受到抑制。因此，似乎非-G-蛋白偶联受体介导的途径对SHIP的异源激活可以影响由独立连接的G-蛋白偶联趋化因子受体激活的PI3K-依赖性信号通路。 （c）2004 Elsevier Inc.保留所有权利。

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