Journal of Molecular Cell Biology, A. Zecchin et al. 2014.
The tyrosine kinase receptor VEGFR2 is a key regulator of angiogenesis interacting primarily with members of the VEGF family, and involving phosphorylation of various tyrosine residues in the intracytoplasmic portion of the receptor. This work provides the first evidence that membrane-associated VEGFR2 in endothelial cells undergoes Lysine acetylation in the kinase insert domain, and in a single lysine located in the receptor activation loop. This demonstrates that VEGFR2 acetylation essentially regulates receptor phosphorylation. While VEGFR2 acetylation counteracts the process of receptor desensitization following VEGF stimulation, it still allows or receptor phosphorylation and intracellular signaling. VEGFR2 mutant cells unable to be acetylated show reduced levels of receptor phosphorylation and impaired migratory capacity. Consistently, MD simulations suggest that acetylation of the lysine in the activation loopcontributes to the transition to an open active state, in which tyrosine phosphorylation is favored by better exposure of the kinase target residues.
