Nj. Pumphrey et al., Differential association of cytoplasmic signalling molecules SHP-1, SHP-2,SHIP and phospholipase C-gamma l with PECAM-1/CD31, FEBS LETTER, 450(1-2), 1999, pp. 77-83
Recent studies have shown that, in addition to its role as an adhesion rece
ptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphoryl
ated on tyrosine residues Y-663 and Y-686 and associates with protein tyros
ine phosphatases SHP-1 and SHP-2, In this study, we screened for additional
proteins which associate with phosphorylated platelet endothelial cell adh
esion molecule 1, using surface plasmon resonance. We found that, besides S
HP-1 and SHP-2, platelet endothelial cell adhesion molecule 1 binds the cyt
oplasmic signalling proteins SHIP and PLC-gamma 1 via their Src homology 2
domains. Using two phosphopeptides, NSDVQpY(663)TEVQV and DTETVpY(686)SEVRK
, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-gamma 1
. All four cytoplasmic signalling proteins directly associate with cellular
platelet endothelial cell adhesion molecule 1, immunoprecipitated from per
vanadate-stimulated THP-1 cells, These results suggest that overlapping imm
unoreceptor tyrosine-based inhibition motif/immunoreceptor tyrosine-based a
ctivation motif-like motifs within platelet endothelial cell adhesion molec
ule 1 mediate differential interactions between the Src homology 2 containi
ng signalling proteins SHP-1, SHP-2, SHIP and PLC-gamma 1. (C) 1999 Federat
ion of European Biochemical Societies.