Interaction of DNAM‐1 induces Poliovirus Receptor phosphorylation and the subsequent recruitment of Shp‐2 to endothelial cell junctions

Abstract

The movement of leukocytes across the endothelium (referred to as Transendothelial Migration or TEM) is a critical step in the inflammatory process and is known to be mediated by PECAM, Poliovirus Receptor (PVR), and CD99. Our new data show that PVR on endothelial cells interacts with DNAX-associated molecule 1 (DNAM-1) on migrating leukocytes at a step in TEM between the steps mediated by PECAM and CD99. Here we show that the pool of PVR that functions in TEM resides in the Lateral Border Recycling Compartment, a recently discovered endothelial cell organelle that is critical to TEM and inflammation. PVR is protected in the LBRC in a fashion similar to PECAM and CD99. Furthermore we show that treating endothelial cells with soluble DNAM-1 induces PVR phosphorylation and subsequent recruitment of the phosphatase Shp-2. Shp-2 has also been shown to interact with PECAM in a phosphorylation-dependent manner. Together, these findings suggest a common mechanism by which intercellular protein interactions between leukocyte and endothelial cells mediate intracellular signals that regulate TEM and, could represent new therapeutic targets for controlling inflammation. This research was supported by F32 AI084454 to DPS and RO1 HL046849 to WAM.