SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages

Curr Biol. 1999 Aug 26;9(16):927-30. doi: 10.1016/s0960-9822(99)80401-1.


Inhibitory immunoreceptors downregulate signaling by recruiting Src homology 2 (SH2) domain-containing tyrosine and/or lipid phosphatases to activating receptor complexes [1]. There are indications that some inhibitory receptors might also perform other functions [2] [3]. In adherent macrophages, two inhibitory receptors, SHPS-1 and PIR-B, are the major proteins binding to the tyrosine phosphatase SHP-1. SHPS-1 also associates with two tyrosine-phosphorylated proteins (pp55 and pp130) and a protein tyrosine kinase [4]. Here, we have identified pp55 and pp130 as the adaptor molecules SKAP55hom/R (Src-kinase-associated protein of 55 kDa homologue) and FYB/SLAP-130 (Fyn-binding protein/SLP-76-associated protein of 130 kDa), respectively, and the tyrosine kinase activity as PYK2. Two distinct SHPS-1 complexes were formed, one containing SKAP55hom/R and FYB/SLAP-130, and the other containing PYK2. Recruitment of FYB/SLAP-130 to SHPS-1 required SKAP55hom/R, whereas PYK2 associated with SHPS-1 independently. Formation of both complexes was independent of SHP-1 and tyrosine phosphorylation of SHPS-1. Finally, tyrosine phosphorylation of members of the SHPS-1 complexes was regulated by integrin-mediated adhesion. Thus, SHPS-1 provides a scaffold for the assembly of multi-protein complexes that might both transmit adhesion-regulated signals and help terminate such signals through SHP-1-directed dephosphorylation. Other inhibitory immunoreceptors might have similar scaffold-like functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation*
  • Bone Marrow Cells / chemistry*
  • COS Cells
  • Cell Adhesion
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • Immunoblotting
  • Macrophages / chemistry*
  • Macrophages / drug effects
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / pharmacology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Neural Cell Adhesion Molecule L1*
  • Neural Cell Adhesion Molecules / metabolism*
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Protein Folding*
  • Protein-Tyrosine Kinases / analysis
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Immunologic*
  • Sulfones / analysis
  • Sulfones / metabolism
  • Uridine / analogs & derivatives
  • Uridine / analysis
  • Uridine / metabolism


  • Antigens, Differentiation
  • Cell Adhesion Molecules
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • Nuclear Proteins
  • Phosphoproteins
  • Ptpns1 protein, mouse
  • Receptors, Immunologic
  • Sulfones
  • nucleolar phosphoprotein p130
  • 5'-O-(((2-decanoylamino-3-phenylpropyloxycarbonyl)amino)sulfonyl)uridine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse
  • Ptk2b protein, mouse
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
  • Uridine