T cell activation through the CD43 molecule leads to Vav tyrosine phosphorylation and mitogen-activated protein kinase pathway activation.
CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signals that lead to Ca2+ mobilization and interleukin-2 production, yet the molecular events involved in signal transduction pathway of the CD43 molecule are only beginning to be understood. We have shown recently that cross-linking CD43 on the cell surface of human T lymphocytes with the anti-CD43 monoclonal antibody L10 leads to CD43-Fyn kinase interactions and to Fyn phosphorylation on tyrosine residues. This interaction seems to be mediated by the SH3 domain of Fyn and a proline-rich sequence located in the cytoplasmic domain of CD43. Here we show that CD43-specific activation of human T lymphocytes induced tyrosine phosphorylation of the adaptor protein Shc and of the guanine exchange factor Vav, as well as the formation of a macromolecular complex that comprises Shc, GRB2, and Vav. CD43 ligation resulted in enhanced formation of Vav.SLP-76 complexes and in the activation and nuclear translocation of ERK2. Cross-linking of the CD43 molecule in 3T3-CD43(+) cells induced luciferase activity from a construct under the control of the Fos serum responsive element. Altogether, these data suggest that the mitogen-activated protein kinase pathway is involved in CD43-dependent interleukin-2 gene expression.
Pedraza-Alva
G
G
Instituto de Biotecnología/UNAM, APDO. Postal 510-3 Cuernavaca, Morelos, 62250, México.
Mérida
L B
LB
Burakoff
S J
SJ
Rosenstein
Y
Y
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015703:Antigens, CD; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D051917:Leukosialin; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D055765:Shc Signaling Adaptor Proteins; D012795:Sialoglycoproteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013601:T-Lymphocytes / Q000502:physiology*; D014162:Transfection / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D003432:Cross-Linking Reagents; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D007376:Interleukin-2; D051917:Leukosialin; D015513:Oncogene Proteins; D011506:Proteins; D051567:Proto-Oncogene Proteins c-vav; C528024:SHC1 protein, human; C465014:SPN protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1