STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells
STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells
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DOI：
10.1016/j.bbrc.2007.05.030
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发表时间：
2007-07-06
影响因子：
3.1
通讯作者：
Matsuda, Tadashi
中科院分区：
文献类型：
--
作者：
Ikeda, Osamu;Sekine, Yuichi;Matsuda, Tadashi
信号转导适配器蛋白-2(STAP-2)是最近发现的一种与c-FMS/M-CSF受体相互作用的适配器蛋白，在巨噬细胞中有成分表达。我们以前的研究还发现，STAP-2与MyD88和IKK-α/β结合，并调节巨噬细胞中的核因子-kappaB信号。在本研究中，我们研究了STAP-2和c-fms之间的相互作用在RAW 264.7巨噬细胞中的生理作用。我们的免疫沉淀显示c-FMS与STAP-2的PH结构域直接相互作用不依赖于M-CSF刺激。STAP-2的异位表达显著抑制M-CSF诱导的c-FMS酪氨酸磷酸化以及Akt和细胞外信号调节激酶的激活。此外，过表达STAP-2的RAW 264.7细胞表现出对M-csf的反应迁移和伤口愈合过程的障碍。综上所述，我们的研究结果表明，STAP-2直接与c-fms结合，并干扰Raw 264.7细胞中导致巨噬细胞运动的PI3K信号。(C)2007 Elsevier Inc.保留所有权利。
Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein as a c-Fms/M-CSF receptor-interacting protein and constitutively expressed in macrophages. Our previous studies also revealed that STAP-2 binds to MyD88 and IKK-alpha/beta, and modulates NF-kappa B signaling in macrophages. In the present study, we examined physiological roles of the interaction between STAP-2 and c-Fms in Raw 264.7 macrophage cells. Our immunoprecipitation has revealed that c-Fms directly interacts with the PH domain of STAP-2 independently on M-CSF-stimulation. Ectopic expression of STAP-2 markedly suppressed M-CSF-induced tyrosine phosphorylation of c-Fms as well as activation of Akt and extracellular signal regulated kinase. In addition, Raw 264.7 cells over-expressing STAP-2 showed impaired migration in response to M-CSF and wound-healing process. Taken together, our findings demonstrate that STAP-2 directly binds to c-Fms and interferes with the PI3K signaling, which leads to macrophage motility, in Raw 264.7 cells. (C) 2007 Elsevier Inc. All rights reserved.