Ligand stimulation of CD155alpha inhibits cell adhesion and enhances cell migration in fibroblasts.
CD155 (poliovirus receptor) localizes in cell-matrix adhesions and cell-cell junctions, but its role in the regulation of cell adhesion and cell motility has not been investigated. We identified a conserved immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic domain of human CD155alpha. The ITIM was tyrosine-phosphorylated upon binding of anti-CD155 monoclonal antibody D171, poliovirus, and DNAM-1 (CD226) to human CD155alpha, and recruited SH2-domain-containing tyrosine phosphatase-2 (SHP-2). After CD155alpha stimulation with its ligands, cell adhesion was inhibited and cell motility was enhanced, effects that were associated with the phosphorylation of ITIM by Src kinases and accompanied by dephosphorylation of focal adhesion kinase and paxillin. These effects were abolished by introducing a point-mutation in Y398F into the ITIM of CD155alpha and by coexpression of a dominant negative SHP-2 mutant with CD155alpha. These results suggest that CD155alpha plays a role in the regulation of cell adhesion and cell motility.
Oda
Toshiyuki
T
Department of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Ohka
Seii
S
Nomoto
Akio
A
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017354:Point Mutation; D020033:Protein Isoforms / Q000378:metabolism*; D054648:Protein Phosphatase 2; D017434:Protein Structure, Tertiary; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; C496062:Pxn protein, mouse; D011991:Receptors, Virus; C066100:poliovirus receptor; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases