Ligand stimulation of CD155α inhibits cell adhesion and enhances cell migration in fibroblasts

Abstract

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 CD155α. The ITIM was tyrosine-phosphorylated upon binding of anti-CD155 monoclonal antibody D171, poliovirus, and DNAM-1 (CD226) to human CD155α, and recruited SH2-domain-containing tyrosine phosphatase-2 (SHP-2). After CD155α 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 CD155α and by coexpression of a dominant negative SHP-2 mutant with CD155α. These results suggest that CD155α plays a role in the regulation of cell adhesion and cell motility.