Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells

J Immunol. 2000 Jan 1;164(1):9-12. doi: 10.4049/jimmunol.164.1.9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation*
  • Cell Line
  • Dendritic Cells / metabolism*
  • Humans
  • Jurkat Cells
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Weight
  • Monocytes / metabolism*
  • Neural Cell Adhesion Molecule L1*
  • Neural Cell Adhesion Molecules / biosynthesis*
  • Neural Cell Adhesion Molecules / metabolism*
  • Neural Cell Adhesion Molecules / physiology
  • Phosphorylation
  • Receptors, Cell Surface
  • Receptors, Immunologic / metabolism*
  • Receptors, Immunologic / physiology
  • Signal Transduction / immunology*
  • U937 Cells

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • SIRPB1 protein, human
  • TYROBP protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases