Abstract
Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-containing protein phosphatase 1 (SHP-1) and SHP-2 and to regulate receptor tyrosine kinase-coupled signaling. One SIRP of unknown function, designated SIRP beta 1, contains a short cytoplasmic domain that lacks sequence motifs capable of recruiting SHP-1 and SHP-2. Using a SIRP-specific mAb, we show that SIRP beta 1 is expressed in monocytes and dendritic cells and associates with the signal transduction molecule DAP12. SIRP beta 1/DAP12 complex formation was required for efficient cell-surface expression of SIRP beta 1. Stimulation of this complex induced tyrosine phosphorylation, mitogen-activated protein kinase activation, and cellular activation. Thus, SIRP beta 1 is a new DAP12-associated receptor involved in the activation of myeloid cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation*
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Cell Line
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Dendritic Cells / metabolism*
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Humans
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Jurkat Cells
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / physiology
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Membrane Proteins
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Weight
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Monocytes / metabolism*
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Neural Cell Adhesion Molecule L1*
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Neural Cell Adhesion Molecules / biosynthesis*
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Neural Cell Adhesion Molecules / metabolism*
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Neural Cell Adhesion Molecules / physiology
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Phosphorylation
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Receptors, Cell Surface
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Receptors, Immunologic / metabolism*
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Receptors, Immunologic / physiology
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Signal Transduction / immunology*
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U937 Cells
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Membrane Glycoproteins
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Membrane Proteins
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Neural Cell Adhesion Molecule L1
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Neural Cell Adhesion Molecules
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Receptors, Cell Surface
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Receptors, Immunologic
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SIRPB1 protein, human
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TYROBP protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases