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Cells can sense when the pressure is on; they respond to fluid shear stress (FSS) by MAPK activation and reorganization of the actin cytoskeleton, for example. Although signaling cascades controlling these changes are well studied, the molecules that sense mechanical stimuli at the plasma membrane are generally unknown. On 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.; p" V! e1 q, X% C% A" o
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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.(Shear stress may cause PECAM-1 phosphory) |
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发表于 2009-3-6 00:14
发表于 2015-5-28 15:16
