The cDNA of a novel mouse cell surface receptor (tie2) has been isolated from a mouse lung library. The predicted amino acid sequence of tie2 encodes a protein of 1122 amino acids, with an extracellular domain and an intracellular tyrosine kinase domain bisected by a transmembrane region. The extracellular domain consists of two Ig-like domains, three cysteine-rich domains and three fibronectin type III repeats whilst the intracellular tyrosine kinase domain has a short insert region of 15 amino acids. In vitro transcription/translation of the tie2 cDNA demonstrates that it encodes a glycoprotein of some 145 kDa. The tie2 protein exhibits a high degree of similarity to the cell surface receptor tie,(Partanen, J. et al.,(1992) Mol. Cell. Biol., 12, 1698-1707), and together with this protein defines a new class of cell surface receptor.