Ikeda Osamu, Sekine Yuichi, Kakisaka Michinori, Tsuji Satoshi, Muromoto Ryuta, Ohbayashi Norihiko, Oritani Kenji, Yoshimura Akihiko, Matsuda Tadashi
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):931-7. doi: 10.1016/j.bbrc.2007.05.030. Epub 2007 May 14.
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-kappaB 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.
信号转导衔接蛋白2（STAP - 2）是最近鉴定出的一种衔接蛋白，作为c - Fms/M - CSF受体相互作用蛋白，在巨噬细胞中组成性表达。我们之前的研究还表明，STAP - 2与MyD88和IKK - α/β结合，并调节巨噬细胞中的NF - κB信号传导。在本研究中，我们研究了Raw 264.7巨噬细胞中STAP - 2与c - Fms相互作用的生理作用。我们的免疫沉淀结果表明，c - Fms在不依赖M - CSF刺激的情况下直接与STAP - 2的PH结构域相互作用。STAP - 2的异位表达显著抑制了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细胞在对M - CSF的反应和伤口愈合过程中迁移受损。综上所述，我们的研究结果表明，在Raw 264.7细胞中，STAP - 2直接与c - Fms结合并干扰PI3K信号传导，这导致了巨噬细胞的运动性。
