Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: is it a mechanoresponsive molecule?

doi:10.1083/jcb.200205049

Published online 12 August 2002. doi:10.1083/jcb.200205049

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© The Rockefeller University Press, 0021-9525/2002/8/773 $5.00
The Journal of Cell Biology, Volume 158, Number 4, August 19, 2002 773-785

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

Fluid shear stress (FSS) induces many forms of responses, includingphosphorylation of extracellular signal–regulated kinase(ERK) in endothelial cells (ECs). We have earlier reported rapidtyrosine phosphorylation of platelet endothelial cell adhesionmolecule-1 (PECAM-1) in ECs exposed to FSS. Osmotic changesalso induced similar PECAM-1 and ERK phosphorylation with nearlyidentical kinetics. Because both FSS and osmotic changes shouldmechanically perturb the cell membrane, they might activatethe same mechanosignaling cascade. When PECAM-1 is tyrosinephosphorylated by FSS or osmotic changes, SHP-2 binds to it.Here we show that ERK phosphorylation by FSS or osmotic changesdepends on PECAM-1 tyrosine phosphorylation, SHP-2 binding tophospho-PECAM-1, and SHP-2 phosphatase activity. In ECs underflow, detectable amounts of SHP-2 and Gab1 translocated fromthe cytoplasm to the EC junction. When magnetic beads coatedwith antibodies against the extracellular domain of PECAM-1were 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 beadsby itself or pulling on the cell surface using poly-L–coatedbeads did not induce phosphorylation of PECAM-1 and ERK. Theseresults suggest that PECAM-1 is a mechanotransduction molecule.

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

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