Functional Hierarchy of the N-Terminal Tyrosines of SLP-76

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 homol...

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Bibliographic Details
Published in:Journal of Immunology 2006-02, Vol.176 (4), p.2430-2438
Main Authors: Jordan, Martha S, Sadler, Jeffrey, Austin, Jessica E, Finkelstein, Lisa D, Singer, Andrew L, Schwartzberg, Pamela L, Koretzky, Gary A
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Calcium - metabolism
Cell Line, Tumor
Enzyme Activation
Humans
Mice
Mitogen-Activated Protein Kinases
Mutation - genetics
NFATC Transcription Factors - metabolism
Phospholipase C gamma - metabolism
Phosphoproteins - chemistry
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphotyrosine - genetics
Phosphotyrosine - metabolism
ras GTPase-Activating Proteins - metabolism
Receptors, Antigen, T-Cell - metabolism
Signal Transduction
Tyrosine - genetics
Tyrosine - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.176.4.2430