PMID- 22120521 OWN - NLM STAT- MEDLINE DCOM- 20120510 LR - 20171116 IS - 1873-3913 (Electronic) IS - 0898-6568 (Linking) VI - 24 IP - 3 DP - 2012 Mar TI - RGS2 is a negative regulator of STAT3-mediated Nox1 expression. PG - 803-9 LID - 10.1016/j.cellsig.2011.11.015 [doi] AB - NADPH oxidase 1 (Nox1) is essential for reactive oxygen species production in the innate immune responses mediated by toll-like receptor (TLR), but the mechanism regulating its expression remains uncertain. Here, we find that Nox1 induction is TLR2-dependent, but independent of myeloid differentiation primary response gene 88 (MyD88). We demonstrate the capacity of signal transducer and activator of transcription 3 (STAT3) to activate Nox1's transcription, as well as cooperative regulation by janus kinase 1 and 3 (JAK1 and JAK3). We find that regulator of G-protein signaling 2 (RGS2) inhibits STAT3-mediated Nox1 transcription, and can itself be repressed by TLR2; Nox1 induction upon RGS2 down-regulation is controlled by protein kinase C-eta (PKC-eta) and phospholipase D2 (PLD2). A GFP-tagged version of RGS2 concentrates in the nucleus; RGS2 additionally directly binds STAT3 to regulate its transcriptional activity through TLR2 stimulation. Cumulatively, these results suggest that TLR2 signaling enhances Nox1 expression through the JAK1/3-STAT3 pathway, and that RGS2, through its regulation by the PKC-eta/PLD2 pathway, represses STAT3's transcriptional activation of Nox1. CI - Copyright (c) 2011. Published by Elsevier Inc. FAU - Lee, Hyung-Kyoung AU - Lee HK AD - Department of Biochemistry & Molecular Biology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Nam-Gu, Daegu, South Korea. FAU - Park, Dae-Weon AU - Park DW FAU - Bae, Jun Ho AU - Bae JH FAU - Kim, Hyung Jun AU - Kim HJ FAU - Shin, Dong-Gu AU - Shin DG FAU - Park, Jong-Seon AU - Park JS FAU - Lee, Jin-Gu AU - Lee JG FAU - Lee, Sung Joong AU - Lee SJ FAU - Bae, Yoe-Sik AU - Bae YS FAU - Baek, Suk-Hwan AU - Baek SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111118 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (RGS Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (STAT3 Transcription Factor) RN - 0 (Toll-Like Receptor 2) RN - EC 1.6.- (NADH, NADPH Oxidoreductases) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 1.6.3.- (NOX1 protein, mouse) RN - EC 2.7.1.- (protein kinase C eta) RN - EC 2.7.10.2 (Janus Kinase 1) RN - EC 2.7.10.2 (Janus Kinase 3) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.- (phospholipase D2) RN - EC 3.1.4.4 (Phospholipase D) SB - IM MH - Animals MH - Cell Line MH - Cell Nucleus/metabolism MH - *Down-Regulation MH - *Gene Expression Regulation, Enzymologic MH - HEK293 Cells MH - Humans MH - Janus Kinase 1/antagonists & inhibitors/genetics/metabolism MH - Janus Kinase 3/antagonists & inhibitors/genetics/metabolism MH - Mice MH - Myeloid Differentiation Factor 88/antagonists & inhibitors/genetics/metabolism MH - NADH, NADPH Oxidoreductases/antagonists & inhibitors/genetics/*metabolism MH - NADPH Oxidase 1 MH - Phospholipase D/antagonists & inhibitors/genetics/metabolism MH - Protein Kinase C/antagonists & inhibitors/genetics/metabolism MH - RGS Proteins/*metabolism MH - RNA Interference MH - RNA, Small Interfering MH - STAT3 Transcription Factor/*metabolism MH - Signal Transduction MH - Toll-Like Receptor 2/antagonists & inhibitors/genetics/metabolism EDAT- 2011/11/29 06:00 MHDA- 2012/05/11 06:00 CRDT- 2011/11/29 06:00 PHST- 2011/10/26 00:00 [received] PHST- 2011/11/07 00:00 [accepted] PHST- 2011/11/29 06:00 [entrez] PHST- 2011/11/29 06:00 [pubmed] PHST- 2012/05/11 06:00 [medline] AID - S0898-6568(11)00361-5 [pii] AID - 10.1016/j.cellsig.2011.11.015 [doi] PST - ppublish SO - Cell Signal. 2012 Mar;24(3):803-9. doi: 10.1016/j.cellsig.2011.11.015. Epub 2011 Nov 18.