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 structurally related putative receptor tyrosine kinases, encoded by distinct genes (tie-1 and tie-2) on mouse chromosome 4. Both tie-1 and tie-2 encode receptor proteins possessing unique multiple extracellular domains: two immunoglobulin-like loop domains flanking three epidermal growth factor repeats followed by three fibronectin-type III repeats. Both genes are expressed in early embryonic vascular system and in maternal decidual vascular endothelial cells, where the vasculature undergoes an active angiogenesis. tie-2, but not tie-1, expression was also detected in extraembryonic mesoderm of the amnion. tie-1, but not tie-2, is expressed in an acute myelogenic cell line in vitro. tie-1 and tie-2 may form another class within the receptor tyrosine kinase gene family, and further characterization of these genes and identification of their putative ligands should define the nature of the signal-transduction cascades underlying early vascular system development, as well as their differential roles in mesodermal, cells of the amniotic and myeloid lineages.