Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Xu, Gang; Shen, Xin; Wai, Christine; Clemmons, David R.

doi:10.1074/jbc.m113.456046

Cited by 43 publications

(54 citation statements)

References 34 publications

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“…ROS can also oxidize cysteine residues of Src, which directly leads to SFK activation. The activation of Src by oxidation is considered to be maintained longer(for at least 3 h)than the activation by phosphorylation (20). In this study, the activity of SFK was sustained for 2 h and the result was consistent with the previous reports.…”

Section: Effect Of Dpi On the P38 Mapk Activity And Expression Of Clasupporting

confidence: 82%

<b>Enhancement of Src Family Kinase Activity is Essential for p38 MAP Kinase-Mediated Dedifferentiation Signal of Parotid Acinar Cells </b>

2016

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Decrease in saliva causes serious problems in clinical dentistry. There have been previous reports on tissue injuries of parotid glands inducing a dedifferentiation signal that causes the loss of function of acinar cells. Since both inhibitors for Src family kinase (SFK) and p38 MAP kinase (p38 MAPK) suppressed the dedifferentiation, SFK-p38 MAPK pathway was considered essential for the signaling. Even though Src and Yes were expressed in the parotid glands, the increase in phosphorylation level was not detected for conserved tyrosine residue in the kinase domain of Src or Yes that promotes kinase activity, following tissue injuries. In this study, the kinase activities were assayed by using the specific substrate for SFK to examine whether the enhancement of kinase activity of SFK was eventuated by tissue injuries. As a result, the activity of the total SFK was elevated after the cellular damage and was sustained for 2 h. To determine the activated SFK member, the SFK activity was examined by immunoprecipitation method with specific antibodies against each SFK member. Elevation of kinase activities of both Src and Yes was detected after cell damages. The elevation ratio of Src activity was higher than Yes, suggesting that the contribution of Src in the dedifferentiation signaling is higher.Diphenyleneiodonium, an NADPH oxidase inhibitor, suppressed the activation of SFK and p38 MAPK, and the expression of claudin-4, a dedifferentiation marker. These results suggest that the activation of SFK is induced by oxidative stresses and is essential for p38 MAPK-mediated dedifferentiation signaling.

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Section: Effect Of Dpi On the P38 Mapk Activity And Expression Of Clasupporting

confidence: 82%

<b>Enhancement of Src Family Kinase Activity is Essential for p38 MAP Kinase-Mediated Dedifferentiation Signal of Parotid Acinar Cells </b>

2016

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“…Src is activated by Nox4-derived ROS elevation to mediate subsequent downstream signaling [22]. In this study, we observed that the phosphorylation of SrcY419 in endothelial cells was increased in a time-dependent manner after 100 mg/L AGEs treatment (Fig.…”

Section: Resultssupporting

confidence: 48%

“…Another study and our present data revealed recruitment of Nox4 to the membrane and subsequent Src activation evoked by the translocation [22]. Moreover, inhibition of oxidative stress attenuated AGE-induced Src phosphorylation.…”

Section: Discussionmentioning

confidence: 83%

“…Moreover, inhibition of oxidative stress attenuated AGE-induced Src phosphorylation. Nox4-derived ROS in cellular oxidative stress is responsible for Src oxidation [32], It has been previously shown that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allows localized ROS generation to mediate sustained Src oxidation and activation [22]. The Src kinase family regulates diverse processes such as cellular differentiation, cell adhesion, migration, and oncogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Mdia1 is Crucial for Advanced Glycation End Product-Induced Endothelial Hyperpermeability

Zhou

Weng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Disruption of endothelial barrier integrity in response to advanced glycation end products (AEGs) stimulation contributes to vasculopathy associated with diabetes mellitus. Mammalian diaphanous-related formin (mDia1) has been reported to bind to the cytoplasmic domain of the receptor for advanced glycation end products (RAGE), which induces a series of cellular processes. This study directly evaluated the participation of mDia1 in AGE-induced hyperpermeability and revealed the precise intracellular signal transductions of this pathological process. Methods: Human umbilical vein endothelial cells (HUVECs) were used in the in vitro studies. Trans-endothelial electric resistance and permeability coefficient for dextran (Pd) were measured to analyze cell permeability. Western blotting, immunofluorescence staining and flow cytometry assay were performed to investigate the underlying mechanism. Dextran flux across the mesentery in mice was monitored to investigate in vivo microvascular permeability. Results: we found that AGEs evoked Nox4 membrane translocation, reactive oxygen species production, phosphorylation of Src and VE-cadherin, dissociation of adherens junctions and eventual endothelial hyperpermeability through RAGE-mDia1 binding. Cells overexpressing mDia1 by recombinant adenovirus infection showed stronger cellular responses induced by AGEs. Down-regulation of mDia1 by infection with an adenovirus encoding siRNA or blockade of RAGE-mDia1 binding by transfection with RAGE mutant plasmids into HUVECs abolished these AGE-induced effects. Furthermore, knockdown of mDia1 using an adenovirus or genetical knockout of RAGE in C57 mice rescued AGE-evoked microvascular hyperpermeability. Conclusion: Our study revealed that mDia1 plays a critical role in AGE-induced microvascular hyperpermeability through binding to RAGE.

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“…By acting as both mutagens and mitogens, ROS is capable of inducing oncogenic transformation and promoting carcinogenesis and is proposed to play major roles in tumor cell transformation, progression, and metastasis (10). Growth factor and mitogenic signals that promote cancer cell growth and survival have been linked to altered mitochondrial functions and generation of ROS (11)(12)(13)(14)(15)(16). However, the molecular mechanism of whether and how the aberrant growth factor/mitogenic signals in tumor cells may control mitochondrial mass and respiration still remains unclear.…”

mentioning

confidence: 99%

Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Signaling Regulates Mitochondrial Biogenesis and Respiration via Estrogen-related Receptor α (ERRα)

Yang

Zeng

et al. 2013

Journal of Biological Chemistry

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Background: Aberrant PTEN/PI3K signaling and mitochondrial abnormalities are commonly associated with cancer. Results: PTEN loss and activation of PI3K/protein kinase B up-regulate ERR␣, increase mitochondrial mass, and induce a metabolic pattern similar to the "Warburg effect." Conclusion: PTEN/PI3K signaling controls mitochondrial mass and function by regulating ERR␣ through the AKT/CREB axis. Significance: This study establishes a novel link between oncogenic signaling and dysregulated mitochondrial metabolism.

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Recruitment of Nox4 to a Plasma Membrane Scaffold Is Required for Localized Reactive Oxygen Species Generation and Sustained Src Activation in Response to Insulin-like Growth Factor-I

Cited by 43 publications

References 34 publications

<b>Enhancement of Src Family Kinase Activity is Essential for p38 MAP Kinase-Mediated Dedifferentiation Signal of Parotid Acinar Cells </b>

<b>Enhancement of Src Family Kinase Activity is Essential for p38 MAP Kinase-Mediated Dedifferentiation Signal of Parotid Acinar Cells </b>

Mdia1 is Crucial for Advanced Glycation End Product-Induced Endothelial Hyperpermeability

Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) Signaling Regulates Mitochondrial Biogenesis and Respiration via Estrogen-related Receptor α (ERRα)

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