The protein-tyrosine phosphatase SHP-2 associates with tyrosine-phosphorylated adhesion molecule PECAM-1 (CD31).
Aggregation of many cell-surface receptors results in tyrosine phosphorylation of numerous proteins. We previously observed the tyrosine phosphorylation of the platelet/endothelial cell adhesion molecule, PECAM-1 (CD31), after FcepsilonRI stimulation in rat basophilic leukemia RBL-2H3 cells. Here we found that PECAM-1 was also transiently tyrosine-phosphoryated after adherence of these cells to fibronectin. Similarly aggregation of the T cell receptor on Jurkat cells also induced this tyrosine phosphorylation. The protein-tyrosine phosphatase SHP-2 is a widely expressed cytosolic enzyme with two Src homology 2 (SH2) domains. SHP-2, but not the related protein-tyrosine phosphatase SHP-1, associated with PECAM-1. This association of the two proteins correlated with the extent of the tyrosine phosphorylation of PECAM-1. A fusion protein containing the two SH2 domains of SHP-2 precipitated PECAM-1 from cell lysates and also directly bound to phosphorylated PECAM-1. In immune precipitate phosphatase assays, there was tyrosine dephosphorylation of PECAM-1. Therefore, integrin and immune receptor activation results in tyrosine phosphorylation of PECAM-1 and the binding of the protein-tyrosine phosphatase SHP-2, which could regulate receptor-mediated signaling in cells.
Sagawa
K
K
Receptors and Signal Transduction Section, OIIB, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kimura
T
T
Swieter
M
M
Siraganian
R P
RP
D000818:Animals; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat