Mechanotransduction PECAM-1 As a Mechanosensor

Endothelial cells (ECs) that line the vasculature are exposed to fluid sheer stress and osmotic stress, conditions that impart mechanical signals. Such signals are transmitted to the cell interior, where changes in cell architecture and gene expression occur in response. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is localized at the junction between ECs and becomes phosphorylated on tyrosine in response to mechanical stimuli. Osawa et al. report that this phosphorylation causes association of PECAM-1 with SHP-2, a phosphatase that activates extracellular signal-regulated kinase (ERK). ERK activation, which has been previously implicated in mechanotransduction, depends on PECAM-1 phosphorylation. The authors propose that in response to mechanical perturbation of the plasma membrane, PECAM-1 becomes phosphorylated by a kinase that has yet to be identified, and then SHP-2 recruitment activates ERK. SHP-2 could subsequently dephosphorylate PECAM-1, but continuous exposure to mechanical stimuli could initiate the phosphorylation cycle again, maintaining the cellular response.

M. Osawa, M. Masuda, K. Kusano, K. Fujiwara, Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: Is it a mechanoresponsive molecule? J. Cell Biol. 158, 773-785 (2002). [Abstract] [Full Text]

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

Masaki Osawa, Michitaka Masuda, Ken-ichi Kusano, and Keigi Fujiwara (19 August 2002)
J. Cell Biol. 158 (4), 773. [DOI: 10.1083/jcb.200205049]
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