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Transactivation of the EGF receptor and a PI3 kinase–ATF‐1 pathway is involved in the upregulation of NOX1, a catalytic subunit of NADPH oxidase
Author(s) -
Fan ChunYuan,
Katsuyama Masato,
Nishinaka Toru,
Yabe-Nishimura Chihiro
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.021
Subject(s) - nox1 , transactivation , signal transduction , microbiology and biotechnology , chemistry , epidermal growth factor , phosphorylation , protein kinase b , protein kinase a , mapk/erk pathway , downregulation and upregulation , cancer research , nadph oxidase , biology , receptor , biochemistry , transcription factor , reactive oxygen species , gene
We previously reported that hypertrophy of vascular smooth muscle cells caused by prostaglandin (PG) F 2α is mediated by the induction of NOX1, a catalytic subunit of NADPH oxidase that generates superoxide. The signal transduction pathway(s) involved in this process, however, remained unresolved. PGF 2α enhanced the phosphorylation of the epidermal growth factor (EGF) receptor, and a selective inhibitor of EGF receptor kinase, tyrphostin AG1478, significantly suppressed PGF 2α ‐induced NOX1 expression. AG1478 also blunted the PGF 2α ‐induced phosphorylation of extracellular signal‐regulated protein kinase (ERK)1/2 and Akt. Phosphoinositide 3 (PI3) kinase inhibitors not only reduced PGF 2α ‐induced NOX1 expression, but also suppressed the phosphorylation of ATF‐1, a transcription factor previously shown to play a key role in the induction of NOX1. Accordingly, the transactivation of the EGF receptor and the activation of ERK1/2, PI3 kinase, and ATF‐1 constitute the signaling pathways involved in the upregulation of NOX1.