Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production
| Autor: | Jun Wu, L. R. Hendricks-Taylor, S E Ross, David G. Motto, Gary A. Koretzky |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
genetic structures
T-Lymphocytes Immunology Molecular Sequence Data Receptors Antigen T-Cell Protein tyrosine phosphatase SH2 domain Lymphocyte Activation Transfection src Homology Domains chemistry.chemical_compound Genes Reporter Immunology and Allergy Humans Amino Acid Sequence Tyrosine Phosphorylation Promoter Regions Genetic Cells Cultured Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Binding Sites biology NFATC Transcription Factors Nuclear Proteins Proteins NFAT Tyrosine phosphorylation Articles equipment and supplies Phosphoproteins Molecular biology Fusion protein eye diseases DNA-Binding Proteins chemistry Gene Expression Regulation Phosphoprotein biology.protein Interleukin-2 GRB2 sense organs Protein Binding Signal Transduction Transcription Factors |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | Recently we described the molecular cloning of SLP-76, a hematopoietic cell-specific 76-kD protein that was first identified through its association with GST/Grb2 fusion proteins. The primary sequence of SLP-76 predicts a protein of 533 amino acids comprising an amino-terminal region with numerous potential tyrosine phosphorylation sites, a central region rich in proline residues, and a single carboxy-terminal SH2 domain. Here we demonstrate formally that Grb2 associates with unphosphorylated SLP-76 and map the Grb2 binding site on SLP-76 undergoes rapid tyrosine phosphorylation and associates with tyrosine phosphoproteins of 36, 62, and 130 kD. In vitro experiments show that the SH2 domain of SLP-76 associates with the 62- and 130-kD proteins and additionally with a serine/threonine kinase. Finally, we demonstrate that transient overexpression of SLP-76 results in dramatically enhanced TCR-mediated induction of nuclear factor of activated T cells (NFAT) and interleukin (IL) 2 promoter activity; and we provide evidence that a functional SLP-76 SH2 domain is required for this effect. Our data document the in vivo associations of SLP-76 with several proteins that potentially participate in T cell activation and implicate SLP-76 itself as an important molecule in TCR-mediated IL-2 production. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|