The Endothelial-specific Receptor Tyrosine Kinase, Tek, is a Member of a New Subfamily of Receptors

We have cloned a 4.2-kb murine cDNA encoding the Tek receptor tyrosine kinase (RTK), which is expressed in endothelial cells and their progenitors. The 1122-residue protein contains an extracellular domain comprising three fibronectin type III repeats fused to two immunoglobulin-like loops that are in turn separated by three epidermal growth factor-like repeats. The association of these different structural motifs and their characteristic arrangement in the Tek extracellular domain has been reported for only one other RTK, Tie, an endothelial-specific RTK of human origin. We show here that Tek and Tie are encoded by distinct genes and that, together, these receptors define a new subfamily of RTKs. In addition, we demonstrate that the tek cDNA, when introduced into COS cells, encodes a product of 140 kDa and that this protein and/or tek transcripts are detectable in highly vascularized embryonic tissues and in some, but not all, cell lines of endothelial origin.