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Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II

Title
Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II
Authors
Choi M.H.Lee I.K.Kim G.W.Kim B.U.Han Y.-H.Yu D.-Y.Park H.S.Kim K.Y.Lee J.S.Choi C.Bae Y.S.Lee B.I.Rhee S.G.Kang S.W.
Ewha Authors
이서구배윤수강상원
SCOPUS Author ID
이서구scopusscopus; 배윤수scopus; 강상원scopus
Issue Date
2005
Journal Title
Nature
ISSN
0028-0836JCR Link
Citation
Nature vol. 435, no. 7040, pp. 347 - 353
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H 2O 2 (refs 1-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H 2O 2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H 2O 2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cγ1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H 2O 2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease.
DOI
10.1038/nature03587
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일반대학원 > 생명·약학부 > Journal papers
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