Role of the CD47-SHPS-1 system in regulation of cell migration.
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.
Motegi
Sei-Ichiro
S
Biosignal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Okazawa
Hideki
H
Ohnishi
Hiroshi
H
Sato
Ryuji
R
Kaneko
Yoriaki
Y
Kobayashi
Hisae
H
Tomizawa
Kyoko
K
Ito
Tomokazu
T
Honma
Nakayuki
N
Bühring
Hans-Jörg
HJ
Ishikawa
Osamu
O
Matozaki
Takashi
T
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation; D001483:Base Sequence; D001665:Binding Sites; D051928:CD47 Antigen; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D006224:Cricetinae; D003432:Cross-Linking Reagents; D003599:Cytoskeleton / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C501920:SIRPA protein, human; C501924:Sirpa protein, rat; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; D020741:rho GTP-Binding Proteins