TIE-1 AND TIE-2 DEFINE ANOTHER CLASS OF PUTATIVE RECEPTOR TYROSINE KINASE GENES EXPRESSED IN EARLY EMBRYONIC VASCULAR SYSTEM

We report the molecular cloning and characterization of two structural ly related putative receptor tyrosine kinases, encoded by distinct gen es (tie-1 and tie-2) on mouse chromosome 4. Both tie-1 and tie-2 encod e receptor proteins possessing unique multiple extracellular domains: two immunoglobulin-like loop domains flanking three epidermal growth f actor repeats followed by three fibronectin-type III repeats. Both gen es are expressed in early embryonic vascular system and in maternal de cidual vascular endothelial cells, where the vasculature undergoes an active angiogenesis. tie-2, but not tie-1, expression was also detecte d in extraembryonic mesoderm of the amnion. tie-1, but not tie-2, is e xpressed in an acute myelogenic cell line in vitro. tie-1 and tie-2 ma y form another class within the receptor tyrosine kinase gene family, and further characterization of these genes and identification of thei r putative ligands should define the nature of the signal-transduction cascades underlying early vascular system development, as well as the ir differential roles in mesodermal, cells of the amniotic and myeloid lineages.