Eph family receptors and ligands in vascular cell targeting and assembly

Members of the Eph family of receptor tyrosine kinases determine neural cell aggregation and targeting behavior functions that are also critical in vascular assembly and remodeling. Among this class of diverse receptors, EphA2 (Eck) and EphB1 (ELK) represent prototypes for two receptor subfamilies distinguished by high-affinity inter-action with either glycerophosphatidylinositol (GPI)-linked or transmembrane ligands, respectively. EphA2 participates in angiogenic responses to tumor necrosis factor (TNF) through an autocrine loop affecting endothelial cell migration. EphB1 and its ligand Ephrin-B1 (LERK-2) are important determinants of assembly of endothelial cells from the microvasculature of the kidney, where both are expressed in endothelial progenitors and in glomerular microvascular endothelial cells. Ephrin-B1 activation of EphB1 promotes assembly of these cells into capillary-like structures. Interaction trap approaches have identified downstream signaling proteins that complex with ligand-activated EphA2 or EphB1, including nonreceptor tyrosine kinases and SH2 domain-containing adapter proteins. The Grb 10 adapter is one of a subset that binds activated EphB1, but not EphA2, defining distinct signaling mechanisms for these related endothelial receptors. On the basis of observations in vascular endothelial cells and recent results defining Eph receptor and ligand roles in neural cell targeting, we propose that these receptors direct cell-cell recognition events that are critical in vasculogenesis and angiogenesis. (C) 1997, Elsevier Science Inc.