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.
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.
Gesbert
F
F
INSERM Unit 461, Faculté de Pharmacie Paris-XI, 92296 Châtenay-Malabry, France.
Guenzi
C
C
Bertoglio
J
J
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases