title: Mechanism of dimerization of a recombinant mature vascular endothelial growth factor C.
abstract: The vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors play a pivotal role in angiogenesis and lymphangiogenesis during development and in pathologies such as tumor growth. The VEGFs function as disulfide-linked antiparallel homodimers. The lymphangiogenic factors, VEGF-C and VEGF-D, exist as monomers and dimers, and dimerization is regulated by a unique unpaired cysteine. In this study, we have characterized the redox state of this unpaired cysteine in a recombinant mature monomeric and dimeric VEGF-C by mass spectrometry. Our findings indicate that the unpaired cysteine regulates dimerization via thiol-disulfide exchange involving the interdimer disulfide bond.
authors.affiliation: Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales , Sydney, NSW 2052, Australia.
authors.forename: Joyce
authors.initials: J
authors.lastname: Chiu
authors.forename: Jason W H
authors.initials: JW
authors.lastname: Wong
authors.forename: Michael
authors.initials: M
authors.lastname: Gerometta
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hogg
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D010084:Oxidation-Reduction; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D004220:Disulfides; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C; D003545:Cysteine