Mechanism of Dimerization of a Recombinant Mature Vascular Endothelial Growth Factor C
journal contributionposted on 2014-01-14, 00:00 authored by Joyce Chiu, Jason W. H. Wong, Michael Gerometta, Philip J. Hogg
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.