Journal of molecular medicine : official organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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Tie2 is expressed predominantly in endothelial cells and is required for blood vessel formation and maintenance. A missense mutation resulting in an R to W substitution in the kinase domain of Tie2 co-segregates with an autosomal dominantly inherited form of vascular dysmorphogenesis, venous malformation (VM). The mechanism by which this activating mutation leads to vessel dysmorphogenesis in VM is not known. ⋯ Dominant-negative Akt inhibited the pro-survival activity of mutant Tie2. Migration of smooth muscle cells induced by conditioned medium from cells expressing mutant receptor was similar to that from cells expressing wild-type receptor. These data suggest that a primary effect of R849W Tie2 in VM is to allow survival of mural cell poor vessels via ligand-independent Tie2 activation of Akt and endothelial survival, rather than to directly induce formation of dysmorphogenic vessels.