| First Author | Jordan MS | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 4 | Pages | 2430-8 |
| PubMed ID | 16456002 | Mgi Jnum | J:129190 |
| Mgi Id | MGI:3768862 | Doi | 10.4049/jimmunol.176.4.2430 |
| Citation | Jordan MS, et al. (2006) Functional hierarchy of the N-terminal tyrosines of SLP-76. J Immunol 176(4):2430-8 |
| abstractText | The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a central role in T cell activation and T cell development. SLP-76 has three functional modules: an acidic domain with three key tyrosines, a central proline-rich domain, and a C-terminal Src homology 2 domain. Of these, mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the most profound effects on T cell development and function. Y112 and Y128 associate with Vav and Nck, two proteins shown to be important for TCR-induced phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin reorganization. Y145 has been shown to be important for optimal association of SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR signaling, cell lines and primary T cells expressing SLP-76 with mutations in individual or paired tyrosine residues were analyzed. These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo. |
