Tie-1 and Tie-2 are receptor tyrosine kinases with unique structural characteristics including two immunoglobulin-like domains flanking three epidermal growth factor (EGF)-like domains, followed by three fibronectin type III-like repeats in the extracellular region, and a split tyrosine kinase domain in the cytoplasmic region. Tie-2 is a receptor for the angiopoietin (ANG) family: ANG-1, ANG-2, and ANG-3 (mouse)/-4 (human). It is involved in vascular stabilization and remodeling. Although less well understood, Tie-1 may also act as an ANG receptor, possibly in complex with Tie-2. Tie-1 is a cell surface protein expressed exclusively in endothelial cells, however it has also been shown to be expressed in immature hematopoietic cells and platelets. Tie-1 upregulates the cell adhesion molecules (CAMs) VCAM-1, E-selectin, and ICAM-1 through a p38-dependent mechanism. Based on gene-targeting studies, the in vivo functions of Tie-1 have been shown to be related to endothelial cell differentiation and the maintenance of integrity of the endothelium. Attachment of monocyte derived immune cells to endothelial cells is also enhanced by Tie-1 expression. Tie-1 has a proinflammatory effect and may play a role in the endothelial inflammatory diseases such as atherosclerosis.