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Publication : Cutting edge: rescue of pre-TCR but not mature TCR signaling in mice expressing membrane-targeted SLP-76.

First Author  Bezman NA Year  2009
Journal  J Immunol Volume  182
Issue  9 Pages  5183-7
PubMed ID  19380761 Mgi Jnum  J:147721
Mgi Id  MGI:3842019 Doi  10.4049/jimmunol.0802176
Citation  Bezman NA, et al. (2009) Cutting edge: Rescue of pre-TCR but not mature TCR signaling in mice expressing membrane-targeted SLP-76. J Immunol 182(9):5183-7
abstractText  SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) organizes signaling from immunoreceptors, including the platelet collagen receptor, the pre-TCR, and the TCR, and is required for T cell development. In this study we examine a mouse in which wild-type SLP-76 is replaced with a mutant constitutively targeted to the cell membrane. Membrane-targeted SLP-76 (MTS) supports ITAM signaling in platelets and from the pre-TCR. Signaling from the mature TCR, however, is defective in MTS thymocytes, resulting in failed T cell differentiation. Defective thymic selection by MTS is not rescued by a SLP-76 mutant whose localization is restricted to the cytosol. Thus, fixed localization of SLP-76 reveals differential requirements for the subcellular localization of signaling complexes downstream of the pre-TCR vs mature TCR.
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