Physical and functional interactions between STAP-2/BKS and STAT5
Physical and functional interactions between STAP-2/BKS and STAT5
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DOI：
10.1074/jbc.m411692200
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发表时间：
2005-03-04
影响因子：
4.8
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Sekine, Y;Yamamoto, T;Matsuda, T
信号转导衔接蛋白家族（Signal-transducing adaptor protein family of proteins，STAPs）目前有两个成员，由于其具有普列克底物蛋白（pleckstrin homology，PH）和Src-同源2（Src-homology 2，SH 2）样结构域而被认为是衔接分子。STAP-1已显示与STAT 5和酪氨酸激酶Tec相互作用。关于STAP-2/BKS功能，免疫沉淀实验和细胞内染色显示STAP-2/BKS在几种类型的细胞中结合STAT 5。突变研究表明，PH-和SH 2-样结构域的STAP-2/BKS与STAT 5的C-末端区域相互作用。STAP-2/BKS和STAT 5被发现组成型共定位于静息细胞的细胞质中，但STAP-2/BKS被发现在STAT 5磷酸化后解离，表明在调节STAT 5的信号传导中的作用。这些相互作用的生理作用尚未完全了解，但在STAP-2/BKS过表达的研究中，精氨酸诱导的酪氨酸磷酸化和STAT 5的转录激活减少。此外，来自STAP-2/BKS缺陷小鼠的胸腺细胞显示增强的白细胞介素-2依赖性细胞生长。总之，STAP-2/BKS是STAT 5介导的信号传导的额外调节剂。
Signal-transducing adaptor protein family of proteins (STAPs), which currently contains two members, are proposed to be adaptor molecules because of their pleckstrin homology (PH) and Src-homology 2 (SH2)-like domains. STAP-1 has been shown to interact with STAT5 and the tyrosine kinase Tec. With regard to STAP-2/BKS functions, immunoprecipitation experiments and intracellular stainings revealed STAP-2/BKS binds STAT5 in several types of cells. Mutational studies revealed that the PH- and SH2-like domains of STAP-2/BKS interacted with the C-terminal region of STAT5. STAP-2/BKS and STAT5 were found to constitutively co-localize in the cytoplasm of resting cells, but STAP-2/BKS was found to dissociate upon STAT5 phosphorylation, suggesting a role in regulating signaling of STAT5. The physiological role of these interactions is not fully understood, but in studies of overexpression of STAP-2/BKS, cytokine-induced tyrosine phosphorylation and transcriptional activation of STAT5 was diminished. In addition, thymocytes from STAP-2/BKS-deficient mice showed the enhanced interleukin-2-dependent cell growth. Taken together, STAP-2/BKS is an additional modulator of STAT5-mediated signaling.