Crucial roles of PECAM-1 in shear stress sensing of vascular endothelial cells

Abstract

Fluid shear stress (FSS) induces many forms of responses, including phosphorylation of ERK in endothelial cells (ECs). We have earlier reported that FSS and hyper-osmotic shock rapidly induce tyrosine phosphorylation of PECAM-1 (CD31). The phosphorylated PECAM-1 acts as a plasma membrane anchoring site for SHP2, a protein tyrosine phosphatase involved in the signal transmission from receptor tyrosine kinases to ERK. Osmotic shock also induces transient ERK activation in ECs. The osmotic-shock-induced ERK activation but not p38 MAP kinase activation was dependent on the PECAM-1 engagement and was blocked by its downregulation. When magnetic beads coated with antibodies against the extracellular domain of PECAM-1 were attached to ECs and tugged by magnetic force, 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-lysine coated beads did not induce phosphorylation of PECAM-1 and ERK. These results suggest that PECAM-1 is a mechanotransduction molecule.