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摘要

The cloning, sequencing and expression of a novel receptor tyrosine kinase, termed tie, is described. The tie precursor comprises 1138 amino acid residues, about 1117 residues of which comprise the mature tie. The tie extracellular domain contains distinct stretches of amino acid sequence having features of the imunoglobulin, epidermal growth factor and fibronectin type III repeat protein families. Alternative splicing creates variants of tie which lack one of the epidermal growth factor homology domains. A specific tyrosine phosphorylated 117 kD glycoprotein is detected by specific tie-antisera from cultured cells expressing the tie gene. The tie mRNA is expressed in cultured endothelial cells as well as in a few tumor cell lines. In situ hybridization of human fetal and mouse embryonic tissues shows specific expression in endothelial cells of blood vessels. The tie DNAs and polypeptides of the invention may be useful in the diagnosis and treatment of certain diseases involving endothelial cells and their tie receptor such as neoplastic diseases involving tumor angiogenesis, wound healing, thromboembolic diseases, atherosclerosis and inflammatory diseases.