Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells

J Immunol. 2001 Feb 1;166(3):1763-70. doi: 10.4049/jimmunol.166.3.1763.


The intracellular Src homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP-1) is a negative regulator of cell signaling and contributes to the establishment of TCR signaling thresholds in both developing and mature T lymphocytes. Although there is much functional data implicating SHP-1 as a regulator of TCR signaling, the molecular basis for SHP-1 activation in T lymphocytes is poorly defined. A modification of the yeast two-hybrid system was employed to identify in T cells phosphotyrosine-containing proteins capable of binding the SH2 domains of SHP-1. From this yeast tri-hybrid screen, the p85beta subunit of phosphatidylinositol 3-kinase and the immunoreceptor tyrosine-based inhibitory motif-containing receptors, leukocyte-associated Ig-like receptor-1 (LAIR-1) and programmed death-1 (PD-1), were identified. Coimmunoprecipitation studies demonstrated that the exclusive phosphotyrosine-containing protein associated with SHP-1 in Jurkat T cells under physiological conditions is LAIR-1. Significantly, this interaction is constitutive and was detected only in the membrane-enriched fraction of cell lysates. Ligand engagement of the SH2 domains of SHP-1 is a prerequisite to activation of the enzyme, and, consistent with an association with LAIR-1, SHP-1 was found to be constitutively active in unstimulated Jurkat T cells. Importantly, a constitutive interaction between LAIR-1 and SHP-1 was also detected in human primary T cells. These results illustrate the sustained recruitment and activation of SHP-1 at the plasma membrane of resting human T cells by an inhibitory receptor. We propose that this mechanism may exert a constitutive negative regulatory role upon T cell signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / immunology
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Catalytic Domain / genetics
  • Catalytic Domain / immunology
  • Cell Fractionation
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cross-Linking Reagents / metabolism
  • Humans
  • Jurkat Cells
  • Mice
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Saponins / pharmacology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / metabolism*
  • Two-Hybrid System Techniques
  • src Homology Domains / genetics
  • src Homology Domains / immunology*


  • Antibodies, Monoclonal
  • Cross-Linking Reagents
  • Phosphoproteins
  • Receptors, Immunologic
  • Saponins
  • leukocyte-associated immunoglobulin-like receptor 1