Roles of the Proline-rich Domain in SLP-76 Subcellular Localization and T Cell Function
| Autor: | Lawrence E. Samelson, Peggy Myung, Amrom E. Obstfeld, Martha S. Jordan, Jennifer N. Wu, Andrew L. Singer, Stephen C. Bunnell, Gary A. Koretzky |
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| Rok vydání: | 2004 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Time Factors genetic structures T-Lymphocytes Lymphocyte Activation Biochemistry Jurkat cells Jurkat Cells Luciferases Genes Dominant Alanine biology Signal transducing adaptor protein Flow Cytometry Cell biology GRB2 Signal transduction Plasmids Signal Transduction Subcellular Fractions Proto-oncogene tyrosine-protein kinase Src Binding domain Proline Blotting Western Arginine Transfection Models Biological Cell Line src Homology Domains Membrane Microdomains Antigens CD Humans Cell Lineage Lectins C-Type Molecular Biology Adaptor Proteins Signal Transducing Lysine Cell Biology Hematopoietic Stem Cells Phosphoproteins equipment and supplies Subcellular localization Precipitin Tests eye diseases Protein Structure Tertiary Phosphoprotein Mutation biology.protein Calcium sense organs Gene Deletion |
| Zdroj: | Journal of Biological Chemistry. 279:15481-15490 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m313339200 |
| Popis: | The adaptor protein Src homology (SH)2 domain-containing and leukocyte-specific phosphoprotein of 76 kDa (SLP-76) is critical for signal transduction in multiple hematopoietic lineages. It links proximal and distal T cell receptor signaling events through its function as a molecular scaffold in the assembly of multimolecular signaling complexes. Here we studied the functional roles of sub-domains within the SLP-76 proline-rich region, specifically the Gads binding domain and the recently defined P1 domain. To gain a further understanding of the functions mediated by this region, we used three complementary approaches as follows: reconstitution of SLP-76-deficient cells with functional domain deletion mutants, blocking molecular associations through the expression of a dominant negative protein fragment, and directed localization of SLP-76 to assess the role of the domains in SLP-76 recruitment. We find the Gads binding domain and the P1 domain are both necessary for optimal SLP-76 function, and in the absence of these two regions, SLP-76 is functionally inert. Furthermore, we provide direct evidence that SLP-76 localization and, in turn, function are dependent upon association with Gads. |
| Databáze: | OpenAIRE |
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