Vav binds to several SH2/SH3 containing proteins in activated lymphocytes.
In T lymphocytes, several proteins are rapidly phosphorylated on tyrosine after stimulation. In this study we examine the ability of tyrosine phosphorylated proteins from Jurkat T cells stimulated by CD2 or T cell receptor-CD3 to interact with the src homology 2 or src homology 3 domains from eight different proteins involved in signal transduction in lymphocytes: Vav, Shc, Nck, phosphatidylinositol-3-kinase, phospholipase C-gamma 1, Ras-GTPase activating protein, c-Crk and Grb2. Our data show that different SH2 domains have distinct patterns of binding to phosphotyrosine containing proteins. We show that Vav, a protein expressed only in hematopoietic cells that may have guanine nucleotide releasing factor activity, is able to interact with certain SH2-containing proteins depending on its tyrosine phosphorylation and with Grb2 in a manner independent of phosphorylation on tyrosine. Coimmunoprecipitation experiments support the idea of a trimolecular complex Shc-Grb2-Vav in vivo. These data suggest a central role played by Vav and provide insight in the complexity and specificity of protein-protein interactions in the signaling events in lymphocytes.
Ramos-Morales
F
F
Institut Cochin de Génétique Moléculaire, U363 INSERM, Hôpital Cochin, Paris, France.
Druker
B J
BJ
Fischer
S
S
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002460:Cell Line; D051380:GRB2 Adaptor Protein; D006801:Humans; D008213:Lymphocyte Activation; D015688:Oncogene Protein pp60(v-src); D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins; C496618:VAV1 protein, human; D014443:Tyrosine; D015688:Oncogene Protein pp60(v-src)