Abstract
Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Antigen Presentation
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Antigen-Presenting Cells / immunology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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CSK Tyrosine-Protein Kinase
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HEK293 Cells
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism
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Humans
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Immunological Synapses / chemistry
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Lymphocyte Activation
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Membrane Microdomains / chemistry
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Membrane Microdomains / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / metabolism*
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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Phosphoproteins / metabolism*
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / metabolism
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RNA Interference
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RNA, Small Interfering
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Signal Transduction
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T-Lymphocytes / immunology*
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src Homology Domains
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src-Family Kinases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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B cell linker protein
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Histocompatibility Antigens Class II
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Membrane Proteins
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Phosphoproteins
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RNA, Small Interfering
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SCIMP protein, human
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SLP-76 signal Transducing adaptor proteins
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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lyn protein-tyrosine kinase
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src-Family Kinases
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CSK protein, human
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Mitogen-Activated Protein Kinases