PROCEEDINGS |
Endothelial cell-cell contact plays importantly in vascular assembly, vessel maturation, specialization and in regulatory control of proliferation and migration. Endothelial cell surface receptors of the EphB family participate importantly in regulating vascular assembly through juxtacrine engagement of their ephrinB ligand partners on contacting cells. Our lab has defined an oligomerization state sensitive molecular switching mechanism in EphB1 receptors that determines alternative downstream responses (Genes & Dev. 12:667, 1998). This receptor activation mechanism functions as a "ligand density sensor" to signal alternative cell-matrix interactions, through a carboxyterminal SAM (sterile alpha motif) domain. Integrin alphavbeta3 is a downstream target activated through distinct convergent pathways we have defined. In complementary work, the endothelial receptor tyrosine phosphatase, CD148, has been assigned a function as a mediator of angiostatic signals, based on monoclonal antibody effects to arrest endothelial growth, migration and corneal angiogenesis. A model for its engagement by ligand on cell-cell contact is proposed. Integration of signals through endothelial cell-cell contact is a critical component of vascular assembly during development and subsequent angiogenesis and remodeling.