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 proge nitors. The 1122-residue protein contains an extracellular domain comp rising 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 an d their characteristic arrangement in the Tek extracellular domain has been reported for only one other RTK, Tie, an endothelial-specific RT K of human origin. We show here that Tek and Tie are encoded by distin ct 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 ti ssues and in some, but not all, cell lines of endothelial origin.