A new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2-induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T lymphocytes
A new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2-induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T lymphocytes
复制标题
DOI：
10.1074/jbc.273.29.18273
复制
发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Bertoglio, J
中科院分区：
文献类型：
--
作者：
Gesbert, F;Guenzi, C;Bertoglio, J
白细胞介素（IL）-2是控制T淋巴细胞分化和增殖的主要细胞因子。在这份报告中，我们的特点是尚未确定的97-kDa的蛋白质，是一个主要的酪氨酸激酶底物在IL-2刺激的细胞。发现pp 97与p85.p110磷脂酰肌醇3-激酶复合物、含Src同源2（SH 2）结构域的酪氨酸磷酸酶SHP-2以及衔接分子CrkL和Grb 2相关。我们证明，这些相互作用是直接介导的CrkL，p85，和SHP-2的SH 2结构域和通过SH 3结构域的Grb 2。发现pp 97介导IL-2诱导的p85与磷酸化和非磷酸化形式的SHP-2之间的相互作用。在这项研究中，我们表明，pp 97的行为作为一个对接蛋白，并与至少CrkL，p85，和SHP-2在同一个多分子复合物。因此，我们的特点pp 97作为一个新的酪氨酸激酶底物在人类T淋巴细胞，可能发挥了重要作用，在调节几个途径激活IL-2。
Interleukin (IL)-2 is a major cytokine that controls differentiation and proliferation of T lymphocytes. In this report we characterize an as yet unidentified 97-kDa protein that is a major tyrosine kinase substrate in IL-2-stimulated cells. pp97 was found to associate with the p85.p110 phosphatidylinositol 3-kinase complex, the Src homology 2 (SH2) domain-containing tyrosine phosphatase SHP-2, and the adaptor molecules CrkL and Grb2. We demonstrate that these interactions are directly mediated through the SH2 domains of CrkL, p85, and SHP-2 and through the SH3 domains of Grb2. pp97 was found to mediate the IL-2-induced interaction between p85 and both a phosphorylated and a non-phosphorylated form of SHP-2. In this study we show that pp97 behaves as a docking protein and associates with at least CrkL, p85, and SHP-2 in the same multimolecular complex. We thus characterized pp97 as a new tyrosine kinase substrate in human T lymphocytes which might play a central role in the regulation of several pathways activated by IL-2.