page 773, Osawa et al. present strong evidence that the adhesion molecule PECAM-1 acts as a mechanosensor and may be a model for other mechanical sensors.PECAM-1 in endothelial cells is known to be phosphorylated rapidly upon sensing changes in FSS. PECAM-1 can then bind to and activate the SHP-2 phosphatase, which dephosphorylates and then falls off PECAM-1. Extracellular signal-related kinase (ERK) is also phosphorylated via RAS signaling under these conditions, activating several genes involved in artherosclerosis. Osawa et al. now show that ERK activation depends on PECAM-1 tyrosine phosphorylation in direct response to mechanical stress.
Phosphorylation was triggered by tugging specifically on PECAM-1, using magnetic beads attached to anti–PECAM-1 antibodies. PECAM-1 molecules are attached to each other on the extracellular side; on the intracellular side, they may be attached to actin via catenin. This double tethering may trap the PECAM-1 molecules so that they cannot move easily in a flexing membrane, leading to distortion and exposure of the tyrosine residues to a nearby kinase. ▪