EXPRESSION OF TIE-2, A MEMBER OF A NOVEL FAMILY OF RECEPTOR TYROSINE KINASES, IN THE ENDOTHELIAL-CELL LINEAGE

We are interested in the molecular mechanisms that are involved in the development of the vascular system. In order to respond to morphogene tic and mitogenic signals, endothelial cells must express appropriate receptors. To characterize endothelial cell-specific receptors, we hav e concentrated on receptor tyrosine kinases, because several lines of evidence suggested the importance of controlled phosphotyrosine levels in endothelial cells. A strategy based on PCR amplification using deg enerate oligonucleotides and mouse brain capillaries as mRNA source, l ed to the identification of a novel receptor tyrosine kinase, which we designated tie-2. In situ hybridization using a tie-2-specific probe revealed, an interesting spatial and temporal expression pattern. The gene was expressed specifically in the endothelial lineage. tie-2 tran scripts were present in endothelial cell precursors (angioblasts) and also in endothelial cells of sprouting blood vessels throughout develo pment and in all organs and tissues so far examined. tie-2 was down-re gulated in the adult. Because of the unusual combination of immunoglob ulin, EGF-like and fibronectin type III domains in the extracellular p ortion of tie-2 which is shared by TEK and tie, these molecules may be considered members of a new family of receptor tyrosine kinases. Sign al transduction via this new class of tyrosine kinases could lead to a better understanding of the molecular mechanisms of blood vessel form ation.