한빛사논문, 상위피인용논문
Abstract
Dong Hoon Kang,1 Doo Jae Lee,1 Kyung Wha Lee,1 Yoon Sun Park,1 Joo Young Lee,1 Sang-Hee Lee,3 Young Jun Koh,4 Gou-Young Koh,4 Chulhee Choi,5 Dae-Yeul Yu,6 Jaesang Kim,1,2 and Sang Won Kang1,2,*
1Division of Life and Pharmaceutical Science, Center for Cell Signaling and Drug Discovery Research
2Department of Life Science, College of Natural Science Ewha Womans University, Seoul 127-750, Korea
3Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, Korea
4Graduate School of Medical Science and Engineering
5Department of Bio and Brain Engineering Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
6Aging Research Center, Korea Research Institute of BioScience and Biotechnology, Daejeon 305-333, Korea
*Correspondence: Sang Won Kang
Summary
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.
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