A NEW TYROSINE-PHOSPHORYLATED 97-KDA ADAPTER PROTEIN MEDIATES INTERLEUKIN-2-INDUCED ASSOCIATION OF SHP-2 WITH P85-PHOSPHATIDYLINOSITOL 3-KINASE IN HUMAN T-LYMPHOCYTES

Interleukin (IL)-2 is a major cytokine that controls differentiation a nd proliferation of T lymphocytes. In this report we characterize an a s yet unidentified 97-kDa protein that is a major tyrosine kinase subs trate in IL-2-stimulated cells. pp97 was found to associate with the p 85.p110 phosphatidylinositol 3-kinase complex, the Src homology 2 (SH2 ) domain-containing tyrosine phosphatase SHP-2, and the adaptor molecu les 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 in teraction between p85 and both a phosphorylated and a non-phosphorylat ed 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 rol e in the regulation of several pathways activated by IL-2.