Platelet-endothelial cell adhesion molecule-1 (CD31), a scaffolding molecule for selected catenin family members whose binding is mediated by different tyrosine and serine/threonine phosphorylation

Platelet-endothelial cell adhesion molecule (PECAM)-1 is a 130-kDa glycopro tein commonly used as an endothelium-specific marker. Evidence to date sugg ests that PECAM-1 is more than just an endothelial cell. marker but is inti mately involved in signal transduction pathways. This is mediated in part b y phosphorylation of specific tyrosine residues within the ITAM domain of P ECAM-1 and by recruitment of adapter and signaling molecules. Recently we d emonstrated that PECAM-1/beta-catenin association functions to regulate bet a-catenin localization and, moreover, to modulate beta-catenin tyrosine pho sphorylation levels. Here we show that: 1) not only beta-catenin, but also gamma-catenin is associated with PECAM-1 in vitro and in vivo; 2) PKC enzym e directly phosphorylates purified PECAM-1; 3) PKC-derived PECAM-1 serine/t hreonine phosphorylation inversely correlates with gamma-catenin associatio n; 4) PECAM-1 recruits gamma-catenin to cell-cell junctions in transfected SW480 cells; and 5) gamma-catenin may recruit PECAM-1 into an insoluble cyt oskeletal fraction. These data further support the concept that PECAM-1 fun ctions as a binder and modulator of catenins and provides a molecular mecha nism for previously reported PECAM-1/cytoskeleton interactions.