TGF-β-induced p38 activation is mediated by Rac1-regulated generation of reactive oxygen species in cultured human keratinocytes

Chiu, Cheuk; Maddock, David Audoen; Zhang, Quanshun; Souza, Kailene P.; Townsend, Amanda; Wan, Yinsheng

doi:10.3892/ijmm.8.3.251

Cited by 32 publications

(35 citation statements)

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“…EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; TGF-b1, transforming growth factor-b1. dramatically inhibited by DPI, suggesting the involvement of NADPH oxidase, consistent with the previous study (Chiu et al, 2001). Furthermore, the activation of this enzyme also required de novo protein synthesis (Figure 5e), implying that some component of this enzyme can be induced by TGF-b1 and control its activity.…”

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

confidence: 75%

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

confidence: 75%

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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“…Activation-Rac1 is one of the subunits of NADPH oxidase and is indispensable for its enzymatic function, namely production of ROS (11), which in turn has been shown to activate p38 in keratinocytes (10). To evaluate the possibility that Rac1 activates p38 and BGN via ROS production through its role as a subunit of NADPH oxidase, we inhibited NADPH oxidase activity using DPI.…”

Section: Dpi a Pharmacologic Inhibitor Of Nadph Oxidase(s) And Herbmentioning

confidence: 99%

“…It was thus not surprising that they have been implicated in TGF-␤ signaling, particularly TGF-␤-induced epithelial-to-mesenchymal transdifferentiation (8), which is known to be associated with p38 activation, increased migration, scattering, and mobilization of the actin cytoskeleton (9). TGF-␤ can also activate p38 through reactive oxygen species (ROS) produced by NAD(P)H oxidase (10), a process that in turn depends on Rac1 as a subunit of this enzyme being absolutely required for its enzymatic activity (for a review, see Ref. 11).…”

mentioning

confidence: 99%

Adhesion and Rac1-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-β

Groth

Schulze

Kalthoff

et al. 2005

Journal of Biological Chemistry

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“…In light of this, one can envision a network of systemic effects mediated by agents that induce the release of IL-6, leading to increased TGF-β levels, which in turn directly or indirectly (via agents like IL-10 (63)) induce the suppression of host responses seen during sepsis. However, little direct evidence is available concerning TGF-β-induced changes either on TGF-β target cell signaling via the SMAD family (64) or p38 MAPK (65) activation and on survival after CLP (Fig. 2).…”

Section: Il-4-thementioning

confidence: 99%

Mechanisms of immune resolution

Ayala

Chung

Grutkoski

et al. 2003

Critical Care Medicine

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Initially after injury, the innate/proinflammatory and some aspects of the acquired immune response are up-regulated to maintain a defense against foreign pathogens, clear tissue debris present at the wound site, and orchestrate aspects of tissue remodeling, cell proliferation and angiogenic process, associated with the wound response. However, for proper wound healing to progress, this initial inflammatory response has to be regulated or shut down so as to allow for the reestablishment of matrix, recellularization, and tissue remodeling. Inability to properly resolve the extent of innate/ acquired response at a site of injury can lead to poor wound healing, immune suppression, and recurrent infectious episodes. This review attempts to summarize information on regulatory mechanisms that are thought to be involved in controlling/resolving innate or acquired immune responses so as to provide a framework for use in thinking about the impact these processes and their manipulation may have on wound healing and its potential management.

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TGF-β-induced p38 activation is mediated by Rac1-regulated generation of reactive oxygen species in cultured human keratinocytes

Cited by 32 publications

References 0 publications

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

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

Adhesion and Rac1-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-β

Mechanisms of immune resolution

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