Peroxiredoxin Il is an essential antioxidant enzyme that prevents the oxidative inactivation of VEGF receptor-2 in vascular endothelial cells

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Title
Peroxiredoxin Il is an essential antioxidant enzyme that prevents the oxidative inactivation of VEGF receptor-2 in vascular endothelial cells
Author(s)
D H Kang; D J Lee; K W Lee; Y S Park; J Y Lee; S H Lee; Y J Koh; G Y Koh; C Choi; Dae Yeul Yu; J Kim; S W Kang
Bibliographic Citation
Molecular Cell, vol. 44, no. 4, pp. 545-558
Publication Year
2011
Abstract
Cellular antioxidant enzymes play crucial roles in aerobic organisms by eliminating detrimental oxidants and maintaining the intracellular redox homeostasis. Therefore, the function of antioxidant enzymes is inextricably linked to the redox-dependent activities of multiple proteins and signaling pathways. Here, we report that the VEGFR2 RTK has an oxidation-sensitive cysteine residue whose reduced state is preserved specifically by peroxiredoxin II (PrxII) in vascular endothelial cells. In the absence of PrxII, the cellular H2O2 level is markedly increased and the VEGFR2 becomes inactive, no longer responding to VEGF stimulation. Such VEGFR2 inactivation is due to the formation of intramolecular disulfide linkage between Cys1199 and Cys1206 in the C-terminal tail. Interestingly, the PrxII-mediated VEGFR2 protection is achieved by association of two proteins in the caveolae. Furthermore, PrxII deficiency suppresses tumor angiogenesis in vivo. This study thus demonstrates a physiological function of PrxII as the residential antioxidant safeguard specific to the redox-sensitive VEGFR2.
ISSN
1097-2765
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.molcel.2011.08.040
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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