Abstract
SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47 and whose cytoplasmic region undergoes tyrosine phosphorylation and there by binds the protein tyrosine phosphatase SHP-2. Formation of this complex is implicated in regulation of cell migration by an unknown mechanism. A CD47-Fc fusion protein or antibodies to SHPS-1 inhibited migration of human melanoma cells or of CHO cells overexpressing SHPS-1. Overexpression of wild-type SHPS-1 promoted CHO cell migration, whereas expression of the SHPS-1-4F mutant, which lacks the phosphorylation sites required for SHP-2 binding, had no effect. Antibodies to SHPS-1 failed to inhibit migration of CHO cells expressing SHPS-1-4F. SHPS-1 ligands induced the dephosphorylation of SHPS-1 and dissociation of SHP-2. Antibodies to SHPS-1 also enhanced Rho activity and induced both formation of stress fibers and adoption of a less polarized morphology in melanoma cells. Our results suggest that engagement of SHPS-1 by CD47 prevents the positive regulation of cell migration by this protein. The CD47- SHPS-1 system and SHP-2 might thus contribute to the inhibition of cell migration by cell-cell contact.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / physiology*
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Antigens, Differentiation*
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Base Sequence
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Binding Sites
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CD47 Antigen
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CHO Cells
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Movement / physiology*
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Cell Size / physiology
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Cricetinae
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Cross-Linking Reagents
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Cytoskeleton / physiology
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DNA, Complementary / genetics
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Humans
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Models, Biological
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Mutation
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Neural Cell Adhesion Molecule L1 / chemistry
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Neural Cell Adhesion Molecule L1 / genetics
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Neural Cell Adhesion Molecule L1 / physiology*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / metabolism
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Rats
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Receptors, Immunologic*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Signal Transduction
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Tumor Cells, Cultured
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Wound Healing / physiology
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rho GTP-Binding Proteins / physiology
Substances
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Antigens, CD
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Antigens, Differentiation
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CD47 Antigen
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CD47 protein, human
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Carrier Proteins
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Cross-Linking Reagents
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DNA, Complementary
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Glycoproteins
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Neural Cell Adhesion Molecule L1
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Receptors, Immunologic
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Recombinant Fusion Proteins
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SIRPA protein, human
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Sirpa protein, rat
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PTPN11 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases
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Ptpn11 protein, rat
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rho GTP-Binding Proteins