title: Emerging roles of post-translational modifications in signal transduction and angiogenesis.
abstract: The vascular endothelial growth factor receptor-2 (VEGFR-2) belongs to the family of receptor tyrosine kinases and is a key player in vasculogenesis and pathological angiogenesis. An emerging picture of PTMs of VEGFR-2 suggests that they play central roles in generating a highly dynamic and complex signaling system that regulates key angiogenic responses ranging from endothelial cell differentiation, proliferation, migration to permeability. Recent MS analysis of VEGFR-2 uncovered previously unrecognized PTMs on VEGFR-2 with a distinct function. The ligand binding extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains highly decorated with N-glycosylation, while its cytoplasmic domain is subject to multiple PTMs including Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation and ubiquitination. Here we review the PTMs on VEGFR-2, their importance in angiogenic signaling relays and possible novel therapeutic potentials.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Rahimi
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Acetylation; Cell biology; Glycosylation; Phosphorylation; Tandem mass spectrometry; VEGF receptor