5gni

Structural highlights

Function

[PECA1_HUMAN] Induces susceptibility to atherosclerosis (By similarity). Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and changes function on apoptosis, promoting tethering of dying cells to phagocytes (the encounter of a viable cell with a phagocyte via the homophilic interaction of PECAM1 on both cell surfaces leads to the viable cell's active repulsion from the phagocyte. During apoptosis, the inside-out signaling of PECAM1 is somehow disabled so that the apoptotic cell does not actively reject the phagocyte anymore. The lack of this repulsion signal together with the interaction of the eat-me signals and their respective receptors causes the attachment of the apoptotic cell to the phagocyte, thus triggering the process of engulfment). Isoform Delta15 is unable to protect against apoptosis. Modulates BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in human umbilical cord vein cells (HUVEC).^{[1] [2] [3]}

References

1. ↑ Brown S, Heinisch I, Ross E, Shaw K, Buckley CD, Savill J. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature. 2002 Jul 11;418(6894):200-3. PMID:12110892 doi:10.1038/nature00811
2. ↑ Bergom C, Paddock C, Gao C, Holyst T, Newman DK, Newman PJ. An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling. J Cell Sci. 2008 Apr 15;121(Pt 8):1235-42. doi: 10.1242/jcs.025163. PMID:18388311 doi:10.1242/jcs.025163
3. ↑ Dasgupta B, Dufour E, Mamdouh Z, Muller WA. A novel and critical role for tyrosine 663 in platelet endothelial cell adhesion molecule-1 trafficking and transendothelial migration. J Immunol. 2009 Apr 15;182(8):5041-51. doi: 10.4049/jimmunol.0803192. PMID:19342684 doi:10.4049/jimmunol.0803192