Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31

Research output: Contribution to journalArticle

Abstract

Recent studies have shown that, in addition to its role as an adhesion receptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphorylated on tyrosine residues Y663 and Y686 and associates with protein tyrosine phosphatases SHP-1 and SHP-2. In this study, we screened for additional proteins which associate with phosphorylated platelet endothelial cell adhesion molecule 1, using surface plasmon resonance. We found that, besides SHP-1 and SHP-2, platelet endothelial cell adhesion molecule 1 binds the cytoplasmic signalling proteins SHIP and PLC-gamma1 via their Src homology 2 domains. Using two phosphopeptides, NSDVQpY663TEVQV and DTETVpY686SEVRK, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-gamma1. All four cytoplasmic signalling proteins directly associate with cellular platelet endothelial cell adhesion molecule 1, immunoprecipitated from pervanadate-stimulated THP-1 cells. These results suggest that overlapping immunoreceptor tyrosine-based inhibition motif/immunoreceptor tyrosine-based activation motif-like motifs within platelet endothelial cell adhesion molecule 1 mediate differential interactions between the Src homology 2 containing signalling proteins SHP-1, SHP-2, SHIP and PLC-gamma1.

Details

Original languageEnglish
Pages (from-to)77-83
JournalFEBS Letters
Volume450
Issue number1-2
Publication statusPublished - 30 Apr 1999

Keywords

  • Phosphotyrosine, Intracellular Signaling Peptides and Proteins, Humans, Surface Plasmon Resonance, Phosphoric Monoester Hydrolases, Amino Acid Sequence, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Binding, Antigens, CD31, src Homology Domains, Binding Sites, Protein Tyrosine Phosphatases, Phospholipase C gamma, SH2 Domain-Containing Protein Tyrosine Phosphatases, Phosphorylation, Isoenzymes, Molecular Sequence Data, Monocytes, Sequence Homology, Amino Acid, Phosphopeptides, Type C Phospholipases, Vanadates, Signal Transduction, Protein Tyrosine Phosphatase, Non-Receptor Type 6