PECAM‐1 isoform‐specific activation of MAPK/ERKs and small GTPases: Implications in inflammation and angiogenesis
- 26 January 2006
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 98 (2) , 451-468
- https://doi.org/10.1002/jcb.20827
Abstract
Platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) is expressed on the surface of endothelial cells (EC) and leukocytes. PECAM-1 plays an important role in endothelial-leukocyte and endothelial-endothelial cell–cell interactions. The anti-PECAM-1 antibody-mediated blockade of these interactions inhibits transendothelial migration (TEM) of leukocytes and angiogenesis. PECAM-1 may accommodate these processes through the regulation of cell adhesive and migratory mechanisms. How PECAM-1 regulates these dynamic processes remain unknown. Here we show that PECAM-1 transduces outside-in signals, which activate MAPK/ERKs and small GTPases. This occurs through PECAM-1-mediated formation of intracellular-signaling complexes, Shc/Grb2/SOS1 and/or Crkl/C3G, which is initiated by PECAM-1 engagement on the surface of leukocytes and/or EC. Src, SHP2, and alternative PECAM-1 pre-mRNA splicing play a regulatory role in these signaling events. Our findings reveal that PECAM-1 engagement on the cell surface can transduce “outside-in” signals and activate MAPK/ERKs and small GTPases, impacting both cadherin-mediated cell–cell and integrin-mediated cell–matrix interactions. Thus, we propose PECAM-1 is an important mediator of vascular barrier and regulator of leukocyte and EC adhesion and migration. J. Cell. Biochem. 98: 451–468, 2006.Keywords
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