Cell
Volume 87, Issue 7, 27 December 1996, Pages 1181-1190
Journal home page for Cell

Article
Vascular Dysmorphogenesis Caused by an Activating Mutation in the Receptor Tyrosine Kinase TIE2

https://doi.org/10.1016/S0092-8674(00)81814-0Get rights and content
Under an Elsevier user license
open archive

Abstract

Venous malformations (VMs), the most common errors of vascular morphogenesis in humans, are composed of dilated, serpiginous channels. The walls of the channels have a variable thickness of smooth muscle; some mural regions lack smooth muscle altogether. A missense mutation resulting in an arginine-to-tryptophan substitution at position 849 in the kinase domain of the receptor tyrosine kinase TIE2 segregates with dominantly inherited VM in two unrelated families. Using proteins expressed in insect cells, we demonstrate that the mutation results in increased activity of TIE2. We conclude that an activating mutation in TIE2 causes inherited VMs in the two families and that the TIE2 signaling pathway is critical for endothelial cell–smooth muscle cell communication in venous morphogenesis.

Cited by (0)