Phosphorylation of serine282 in NADPH oxidase activator 1 by Erk desensitizes EGF-induced ROS generation

Oh, Hyunjin; Jung, Hye Young; Kim, Jaesang

doi:10.1016/j.bbrc.2010.03.053

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…6A). Then, as extracellular signal‐regulated kinase (ERK) is the major mitogenic pathway initiated by EGFR activation (Blenis, 1993; Marshall, 1995) and is implicated in the regulation of EGF‐induced ROS generation (Oh et al, 2010), we treated cells with the specific ERK inhibitor PD98059 (20 µM, 1 h) before UVA irradiation (9 J/cm 2 ). ERK inhibition also increased UVA‐ROS production in HaCaT‐MC1R cells, but not in the parental HaCaT and HaCaT‐R 151 C cell lines (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Since recent findings demonstrate that Ser 282 of NoxA1 is phosphorylated by ERK in response to EGF (Kroviarski et al, 2010; Oh et al, 2010), we asked whether EGFR/ERK inhibition could affect PKA‐dependent NoxA1 phosphorylation in MC1R‐transfected HaCaT cells. To this aim, HaCaT MC1R cells (clone 53) were treated with 0.5 µM PD153035 (EGFR inhibitor) for 1 h or with 20 µM PD98059 (ERK inhibitor) for 1 h. Then, NoxA1 was immunoprecipitated and its phosphorylation status was determined by immunoblotting with an anti‐phospho‐(Ser/Thr) PKA substrate antibody.…”

Section: Resultsmentioning

confidence: 99%

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MC1R expression in HaCaT keratinocytes inhibits UVA‐induced ROS production via NADPH Oxidase‐ and cAMP‐dependent mechanisms

Henri

Beaumel

Guezennec

et al. 2012

Journal Cellular Physiology

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Ultraviolet A (UVA) radiations are responsible for deleterious effects, mainly due to reactive oxygen species (ROS) production. Alpha-melanocyte stimulating hormone (α-MSH) binds to melanocortin-1 receptor (MC1R) in melanocytes to stimulate pigmentation and modulate cutaneous inflammatory responses. MC1R may be induced in keratinocytes after UV exposure. To investigate the effect of MC1R signaling on UVA-induced ROS (UVA-ROS) production, we generated HaCaT cells that stably express human MC1R (HaCaT-MC1R) or the Arg151Cys (R(151)C) non-functional variant (HaCaT-R(151)C). We then assessed ROS production immediately after UVA exposure and found that: (1) UVA-ROS production was strongly reduced in HaCaT-MC1R but not in HaCaT-R(151)C cells compared to parental HaCaT cells; (2) this inhibitory effect was further amplified by incubation of HaCaT-MC1R cells with α-MSH before UVA exposure; (3) protein kinase A (PKA)-dependent NoxA1 phosphorylation was increased in HaCaT-MC1R compared to HaCaT and HaCaT-R(151)C cells. Inhibition of PKA in HaCaT-MC1R cells resulted in a marked increase of ROS production after UVA irradiation; (4) the ability of HaCaT-MC1R cells to produce UVA-ROS was restored by inhibiting epidermal growth factor receptor (EGFR) or extracellular signal-regulated kinases (ERK) activity before UVA exposure. Our findings suggest that constitutive activity of MC1R in keratinocytes may reduce UVA-induced oxidative stress via EGFR and cAMP-dependent mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

MC1R expression in HaCaT keratinocytes inhibits UVA‐induced ROS production via NADPH Oxidase‐ and cAMP‐dependent mechanisms

Henri

Beaumel

Guezennec

et al. 2012

Journal Cellular Physiology

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“…The regulatory subunit p47 phox , which can influence the activities of Nox1, 2, and 3, has been shown to be phosphorylated by ERK1/2 on S345, and this modification promotes increased Nox2 activity (16). Other Nox regulatory subunits that can be targeted by ERK include Nox organizer 1 and Nox activator 1, which regulate the activities of both Nox1 and Nox3 (30,37). These effects are not limited to ERK, and other MAPKs such as p38 MAPK can also influence p47 phox phosphorylation and Nox2 activity (16).…”

Section: Discussionmentioning

confidence: 98%

Molecular regulation of NADPH oxidase 5 via the MAPK pathway

Pandey

Fulton

2011

American Journal of Physiology-Heart and Circulatory Physiology

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The mechanisms controlling the activity of NADPH oxidase 5 (Nox5) are unique in that they are independent of the protein: protein interactions that coordinate the activation of other Nox isoforms. Instead, the primary driving force for Nox5 activity is calcium. However, in a previous study we reported that the protein kinase C (PKC)-agonist PMA could induce a sustained activation of Nox5 that was independent of calcium changes. This apparent calcium-independent activation was found to be mediated by the PKC-dependent phosphorylation of specific serine and threonine residues on Nox5 which increased the calcium sensitivity of the enzyme and enabled activation at resting levels of calcium. However, the specific kinase(s) mediating the phosphorylation and activation of Nox5 are not known. As PKC can activate the MEK/ERK1/2 signaling pathway, we hypothesized that Nox5 is activated by the coordinated phosphorylation of both MAPK and PKC pathways. The inhibition of MEK1 using PD-98059 and U-0126 significantly reduced the phosphorylation and activity of Nox5 in response to PMA but not to the calcium-mobilizing stimulus ionomycin. Dominant negative MEK1 and knockdown of endogenous MEK1/2 using a specific small interfering RNA also inhibited Nox5 activity in response to PMA. The mutation of S498 to a nonphosphorylatable residue and to a lesser degree T494 blocked the ability of ERK to stimulate Nox5 activity. However, a constitutively active form of MEK1 failed to increase Nox5 activity in the absence of PMA stimulation. These results suggest that the MEK/ERK1/2 pathway is necessary but not sufficient to regulate the PMA-dependent activation of Nox5.

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“…βPix siRNA-based knockdown experiments block EGF-induced H 2 O 2 production and Rac1 activation. A separate study reports Nox1 is negatively modulated during EGF signaling by phosphorylation of Ser282 of Nox activator 1 (NOXA1, a Nox1 subunit) by Erk1/2 and Ser172 by PKC to prevent hyperactivation (Oh et al, 2010, Kroviarski et al, 2010). Nox4 is another isoform that regulates EGFR in a spatially dependent manner through PTP1B inactivation (Chen et al, 2008).…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Redox regulation of protein kinases

Truong

Carroll

2013

Critical Reviews in Biochemistry and Molecular Biology

143

101

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Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses.

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Phosphorylation of serine282 in NADPH oxidase activator 1 by Erk desensitizes EGF-induced ROS generation

Cited by 15 publications

References 24 publications

MC1R expression in HaCaT keratinocytes inhibits UVA‐induced ROS production via NADPH Oxidase‐ and cAMP‐dependent mechanisms

MC1R expression in HaCaT keratinocytes inhibits UVA‐induced ROS production via NADPH Oxidase‐ and cAMP‐dependent mechanisms

Molecular regulation of NADPH oxidase 5 via the MAPK pathway

Redox regulation of protein kinases

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