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J. Cell Biol. 158 (4): 773-785

Copyright © 2002 by the Rockefeller University Press.


Article

Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction

is it a mechanoresponsive molecule?

Masaki Osawa1,3, Michitaka Masuda1, Ken-ichi Kusano2, and Keigi Fujiwara3

1 Department of Structural Analysis, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
2 Molecular Cell Science Laboratory, RIKEN, Saitama 351-0198, Japan
3 Center for Cardiovascular Research, University of Rochester, Rochester, NY 14642

Address correspondence to K. Fujiwara, Center for Cardiovascular Research, University of Rochester, 601 Elmwood Ave., Box 679, Roches-ter, NY 14642. Tel.: (716) 273-5714. Fax: (716) 273-1497. E-mail: keigi_fujiwara{at}urmc.rochester.edu

Abstract: Fluid shear stress (FSS) induces many forms of responses, including phosphorylation of extracellular signal–regulated kinase (ERK) in endothelial cells (ECs). We have earlier reported rapid tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in ECs exposed to FSS. Osmotic changes also induced similar PECAM-1 and ERK phosphorylation with nearly identical kinetics. Because both FSS and osmotic changes should mechanically perturb the cell membrane, they might activate the same mechanosignaling cascade. When PECAM-1 is tyrosine phosphorylated by FSS or osmotic changes, SHP-2 binds to it. Here we show that ERK phosphorylation by FSS or osmotic changes depends on PECAM-1 tyrosine phosphorylation, SHP-2 binding to phospho-PECAM-1, and SHP-2 phosphatase activity. In ECs under flow, detectable amounts of SHP-2 and Gab1 translocated from the cytoplasm to the EC junction. When magnetic beads coated with antibodies against the extracellular domain of PECAM-1 were attached to ECs and tugged by magnetic force for 10 min, PECAM-1 associated with the beads was tyrosine phosphorylated. ERK was also phosphorylated in these cells. Binding of the beads by itself or pulling on the cell surface using poly-L–coated beads did not induce phosphorylation of PECAM-1 and ERK. These results suggest that PECAM-1 is a mechanotransduction molecule.

Key Words: mechanosignal transduction; shear stress; ERK; SHP-2; Gab1


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