Differential association of cytoplasmic signalling molecules SHP‐1, SHP‐2, SHIP and phospholipase C‐γ1 with PECAM‐1/CD31

FEBS Letters

Freeman, Sylvie⁴  Wakelam, Michael J.O.³  Young, Stephen P.¹  Taylor, Vanessa⁴  Lord, Janet M.¹  Bird, Ian N.²  Bradfield, Paul F.¹  Pumphrey, Nicholas J.¹  Douglas, Michael R.¹  Salmon, Michael¹  Buckley, Christopher D.¹ 

[1] Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK;Yamanouchi Research Institute, Littlemore Park, Oxford OX4 4SX, UK;Division of Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK;Cell Adhesion Laboratory, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK

关键词: Platelet endothelial cell adhesion molecule 1;    Surface plasmon resonance;    Protein-protein interaction;    Src homology 2 domain;    SH2;    Src homology 2;    GST;    glutathione-S-transferase;    ITAM;    immunoreceptor tyrosine-based activation motif;    ITIM;    immunoreceptor tyrosine-based inhibition motif;    PTK;    protein tyrosine kinase;    PECAM-1;    platelet endothelial cell adhesion molecule 1;    N;    NH2-terminal;    C;    COOH-terminal;    NC;    NH2- and COOH-terminal;    pY;    phosphotyrosine;    PDGF;    platelet derived growth factor;   

DOI  :  10.1016/S0014-5793(99)00446-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-γ1 via their Src homology 2 domains. Using two phosphopeptides, NSDVQpY⁶⁶³TEVQV and DTETVpY⁶⁸⁶SEVRK, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-γ1. 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-γ1.

【 授权许可】

Unknown