EGF blocks NADPH oxidase activation by TGF‐β in fetal rat hepatocytes, impairing oxidative stress, and cell death

Carmona-Cuenca, Irene; Herrera, Blanca; Ventura, Juan-José; Roncero, César; Fernández, Margarita; Fabregat, Isabel

doi:10.1002/jcp.20568

Cited by 70 publications

(66 citation statements)

References 52 publications

(85 reference statements)

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“…Src-TYKs are known to upregulate PI3K through multiple mechanisms including recruitment of PI3K to activated membrane compartments, activation of the p85 PI3K regulatory subunit, and inhibition of the lipid phosphatase PTEN (2,9,38,48). Our data provide some insight into the mechanism of action of Src-TYK.…”

Section: Discussionmentioning

confidence: 69%

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cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

Gates¹,

Hohenester²,

Anwer³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Discussionmentioning

confidence: 69%

“…Src tyrosine kinases (Src-TYK) are a family of kinases several of which are ubiquitously expressed (60). In nonhepatic cells, cAMP can activate Src-TYK (30), and Src-TYK are known to upregulate PI3K/Akt signaling (2,9,38,39,48). In addition, Src-TYK are well-known prosurvival signaling molecules in many cell types including hepatocytes (5,14,44,55).…”

mentioning

confidence: 99%

cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

Gates¹,

Hohenester²,

Anwer³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…NADPH oxidase consists of two membranespanning subunits: p22phox, which is thought to serve as a stabilizing and regulatory subunit for gp91phox (Nox2) and the superoxide producing subunit and its homologues Nox1 and Nox4. The cytoplasmic components of the oxidase, p47phox and p67phox, as well as Rac (Rac1 or Rac2) are thought to regulate the assembly of the functional oxidase, and thus, also its activity (Rocic and Lucchesi, 2005), and they are inducible (Carmona-Cuenca et al, 2005). We therefore propose that activation of NADPH oxidase through de novo synthesis of a component of this enzyme may result in a delayed EGFR/ERK activation.…”

Section: Egfr Transactivation Is Important For Expression Of C-fos Anmentioning

confidence: 96%

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-β involves multiple signaling pathways

et al. 2007

Oncogene

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Many of the signaling responses induced by transforming growth factor-b (TGF-b) are mediated by Smad proteins, but there is evidence that it can also signal independently of Smads. Here, we provide evidence that multiple signal pathways induced by TGF-b1-including Src family tyrosine kinases (SFKs), generation of reactive oxygen species (ROS), de novo protein synthesis and E-cadherindependent cell-cell interactions-transactivate the epidermal growth factor receptor (EGFR), which in turn regulates expression of c-Fos and c-Jun. Immunoprecipitation and immunofluorescence staining showed that EGFR was phosphorylated on tyrosine in response to TGF-b1. EGFR transactivation required the activation of SFKs and the production of ROS via NADPH oxidase, but was not dependent on metalloproteases or the release of EGF-like ligands. In addition, the production of ROS was dependent on signaling by specific SFKs as well as de novo protein synthesis. Stable transfection of E-cadherin into MDA-MB-231 cells as well as E-cadherin-blocking assays revealed that E-cadherin-mediated cell-cell interactions were also essential for EGFR transactivation. Finally, EGFR transactivation was involved in the expression of c-Fos and c-Jun via the extracellular signal-regulated kinase signaling cascade. Taken together our data suggest that ligand release-independent transactivation of EGFR may diversify early TGF-b signaling and represent a novel pathway leading to TGF-b-mediated gene expression.

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“…These factors, which may include parasite GPI, mammalian insulin or IGF, and mosquito NO and ILPs, may function synergistically along a dose-response continuum or they may act antagonistically so that the resource-intensive physiologies of reproduction and immunity are coordinately fine-tuned to maximize the benefits of blood feeding. Further, in mammals and nematodes, a second evolutionarily conserved growth factor signaling pathway regulated by the transforming growth factor (TGF)-βs, a large superfamily of proteins that includes growth factors and immunomodulatory cytokines, extensively intersects the insulin signaling pathway to regulate aging, oxidative stress, and immunity [69][70][71][72][73]. Like the insulin signaling pathway, the TGF-β signaling pathway regulates the NO-dependent immune response in An.…”

Section: Insulin Signaling and Its Impact On Malaria Transmissionmentioning

confidence: 99%

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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As revealed over the past twenty years, the insulin signaling cascade plays a central role in regulating immune and oxidative stress responses that affect the life spans of mammals and two model invertebrates, the nematode Caenorhabitis elegans and the fruit fly Drosophila melanogaster. In mosquitoes, insulin signaling regulates key steps in egg maturation and immunity and likely affects aging, although the latter has yet to be examined in detail. Reproduction, immunity and aging critically influence the capacity of mosquitoes to effectively transmit malaria parasites. Current work has demonstrated that molecules from the invading parasite and the blood meal elicit functional responses in female mosquitoes that are regulated through the insulin signaling pathway or by crosstalk with interacting pathways. Defining the details of these regulatory interactions presents significant challenges for future research, but will increase our understanding of mosquito/malaria parasite transmission and of the conservation of insulin signaling as a key regulatory nexus in animal biology. Keywordsinsulin; Anopheles; Plasmodium; mosquito; malaria; aging; oxidative stress; innate immunity; nitric oxide; transforming growth factor; β In all well-studied metazoans, metabolism, growth, and longevity are coordinately regulated via a nexus that involves signaling cascades activated by insulin and insulin-like growth factors (IGF). Although these pathways differ in downstream physiological effects and some of their signaling proteins, the proteins themselves and their scaffolding interactions are largely conserved among model organisms ( Fig. 1), particularly in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse Mus musculus. This review will examine our current understanding of how the insulin and IGF signaling cascades (ISC) regulate immunity in these diverse model organisms. In addition, we will explore how recent Correspondence to: Shirley Luckhart. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Key targets of daf-16 regulation include genes for mitochondrial manganese superoxide dismutase (MnSOD) and glutathione S-transferase, which are closely linked to aging in C. elegans and other organisms, and genes for numerous C-type lectins, which play critical roles in cell adhesion and pathogen recognition [5]. Downregulation of these gene targets in daf-16 mutants would be predicted to enhance oxidative stress, which has been linked directly to aging in C. elegans [6,7], and decrease pathogen recognition [8]. Conversely, rescue of downregulated MnSOD...

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EGF blocks NADPH oxidase activation by TGF‐β in fetal rat hepatocytes, impairing oxidative stress, and cell death

Cited by 70 publications

References 52 publications

cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-β involves multiple signaling pathways

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

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