Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / biosynthesis*
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / physiology
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Membrane / genetics
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Cell Membrane / immunology
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Cell Membrane / metabolism*
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Gene Knock-In Techniques
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Gene Targeting
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Humans
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Jurkat Cells
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Phosphoproteins / biosynthesis*
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Phosphoproteins / genetics*
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Phosphoproteins / physiology
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Protein Precursors / biosynthesis
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Protein Precursors / genetics
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Protein Precursors / physiology*
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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LAT protein, human
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Membrane Glycoproteins
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Membrane Proteins
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Phosphoproteins
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Protein Precursors
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Receptors, Antigen, T-Cell, alpha-beta
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SLP-76 signal Transducing adaptor proteins
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pre-T cell receptor alpha