A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction. J Immunol 1999 Jul 15;163(2):682-8
Date
07/08/1999Pubmed ID
10395658Scopus ID
2-s2.0-0033565294 (requires institutional sign-in at Scopus site) 142 CitationsAbstract
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa transmembrane glycoprotein expressed by endothelial cells, platelets, monocytes, neutrophils, and certain T cell subsets. The PECAM-1 extracellular domain has six Ig-homology domains that share sequence similarity with cellular adhesion molecules. The PECAM-1 cytoplasmic domain contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) that, when appropriately engaged, becomes phosphorylated on tyrosine residues, creating docking sites for nontransmembrane, Src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-1 and SHP-2. The purpose of the present study was to determine whether PECAM-1 inhibits protein tyrosine kinase (PTK)-dependent signal transduction mediated by the immunoreceptor tyrosine-based activation motif-containing TCR. Jurkat cells, which coexpress PECAM-1 and the TCR/CD3 complex, were INDO-1AM-labeled and then incubated with anti-CD3epsilon mAbs, anti-PECAM-1 mAbs, or both, and goat anti-mouse IgG was used to cross-link surface-bound mAbs. Calcium mobilization induced by CD3 cross-linking was found to be attenuated by coligation of PECAM-1 in a dose-dependent manner. PECAM-1-mediated inhibition of TCR signaling was attributable, at least in part, to inhibition of release of calcium from intracellular stores. These data provide evidence that PECAM-1 can dampen signals transduced by ITAM-containing receptors and support inclusion of PECAM-1 within the family of ITIM-containing inhibitors of PTK-dependent signal transduction.
Author List
Newton-Nash DK, Newman PJAuthor
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
CalciumCell Line, Transformed
Humans
Immunosuppressive Agents
Intracellular Fluid
Jurkat Cells
Lymphocyte Activation
Phosphorylation
Platelet Endothelial Cell Adhesion Molecule-1
Protein Tyrosine Phosphatases
Receptors, Antigen, T-Cell
Signal Transduction
T-Lymphocytes
Tyrosine
