Tie-1 and Tie-2 (also designated Tek) are novel cell surface receptor tyrosine kinases. The extracellular domain of Tie-1 has an unusual multidomain structure consisting of a cluster of three epidermal growth factor homology motifs localized between two immunoglobulin-like loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Angiopoietin-1 (Ang-1) is a secreted ligand for Tie-2. Preliminary biochemical analyses of Ang-1 reveal a potential fibrinogen-like domain at the carboxy terminus and coiled-coil regions in the amino terminus. Ang-1 is an angiogenic factor that is thought to be involved in endothelial development. A related protein, angiopoietin-2 (Ang-2), has been identified as a naturally occurring antagonist of Ang-1 activation of Tie-2.