期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 9, 页码 5183-5187出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802176
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资金
- Howard Hughes Medical Institute
- American Heart Association
- Arthritis Foundation
- National Institutes of Health
- Abramson Family Cancer Research Institute
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 NITS 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. The Journal of Immunology, 2009,182:5183-5187.
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