A Tie2 kinase mutation causing venous malformations increases phosphorylation rates and enhances cooperativity.

ABSTRACT: The endothelial receptor tyrosine kinase Tie2 plays an important role in vascular formation and maintenance. Mutations in Tie2 lead to vascular malformations, which are painful vascular lesions that cause disfigurement, bleeding, and thrombosis. R849W Tie2 is the most common mutation implicated in an inherited form of vascular malformations and has been shown to be activating, though little is known about the kinetic features of catalysis. Here we undertake a steady-state kinetic analysis of heterologously expressed and purified wild type (WT) and R849W Tie2. While the catalytic efficiencies of the two forms are not significantly different, the observed maximal rate of phosphorylation, k_cat,obs, is > 3-fold higher for R849W Tie2 compared to WT. Notably, steady-state catalysis by

SUBMITTER: Kennedy MA 

PROVIDER: S-EPMC6348033 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature