Involvement of growth factor receptors in the mammalian UVC response

doi:10.1016/0092-8674(94)90272-0

Cell

Volume 78, Issue 6, 23 September 1994, Pages 963-972

https://doi.org/10.1016/0092-8674(94)90272-0 Get rights and content

Abstract

Irradiation of HeLa cells with short-wavelength ultraviolet light (UVC) induces the modification and activation of the preexisting transcription factors c-Fos-c-Jun (AP-1) and TCF/EIk-1, as well as the protein synthesis independent transcriptional activation of the c-fos and c-jun genes. This response to UVC is mediated via obligatory cytoplasmic signal transduction, involving Ras and Raf, Src, and MAP kinases. The UVC response is inhibited by prior down-modulation of growth factor receptor signaling upon growth factor prestimulation, by suramin (an inhibitor of receptor activation) or by expression of a dominant negative epidermal growth factor (EGF) receptor mutant. These data suggest the involvement of several growth factor receptors in the UVC response. Indeed, UVC induces the suramin-inhibitable immediate tyrosine phosphorylation of the EGF receptor.

References (53)

S. Andersson et al.
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme
J. Biol. Chem.
(1989)
T.G. Boulton et al.
ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF
Cell
(1991)
W.J. Boyle et al.
Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity
Cell
(1991)
C. Cochet et al.
C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity
J. Biol. Chem.
(1984)
B. Dérijard et al.
JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Cell
(1994)
Y. Devary et al.
The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases
Cell
(1992)
S.S. Huang et al.
Rapid turnover of the platelet-derived growth factor receptor in sis-transformed cells and reversal by suramin
J. Biol. Chem.
(1988)
C. Jonat et al.
Anti-tumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone
Cell
(1990)
A.S. Kraft et al.
Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells
J. Biol. Chem.
(1982)
M. Krämer et al.
UV-irradiation-induced interleukin-1 and basic fibroblast growth factor synthesis and release mediate part of the UV response
J. Biol. Chem.
(1993)

R. Marais et al.

The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain

Cell

(1993)

B. Margolis et al.

EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling

Cell

(1989)

D.J. Robbins et al.

Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro

J. Biol. Chem.

(1993)

C. Sachsenmaier et al.

Damage to DNA by UV light and activation of transcription factors

Biochem. Pharmacol.

(1994)

J. Schlessinger

How receptor tyrosine kinases activate Ras

Trends Biochem. Sci.

(1993)

J. Schlessinger et al.

Growth factor signaling by receptor tyrosine kinases

Neuron

(1992)

M. Schorpp et al.

UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells

Cell

(1984)

P.E. Shaw et al.

The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter

Cell

(1989)

R. Treisman

Ternary complex factors: growth factor regulated transcriptional activators

Curr. Opin. Genet. Dev

(1994)

D.B. Yarosh et al.

Cyclobutane pyrimidine dimers in UV-DNA induce release of soluble mediators that activate the human immunodeficiency virus promoter

J. Invest. Dermatol.

(1993)

P. Angel et al.

12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region

Mol. Cell. Biol.

(1987)

C. Betsholtz et al.

Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin

M. Büscher et al.

Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element

Oncogene

(1988)

Y. Devary et al.

Rapid and preferential activation of the c-jun gene during the mammalian UV response

Mol. Cell. Biol.

(1991)

Y. Devary et al.

NF-κB activation by ultraviolet light not dependent on a nuclear signal

Science

(1993)

K.A.O. Ellem et al.

UVR induction of TGFα: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis

Carcinogenesis

(1988)

Cited by (416)

The role of EGFR in vascular AT1R signaling: From cellular mechanisms to systemic relevance
2023, Biochemical Pharmacology
The epidermal growth factor receptor (EGFR) belongs to the ErbB-family of receptor tyrosine kinases that are of importance in oncology. During the last years, substantial evidence accumulated for a crucial role of EGFR concerning the action of the angiotensin II type 1 receptor (AT1R) in blood vessels, resulting form AT1R-induced EGFR transactivation. This transactivation occurs through the release of membrane-anchored EGFR-ligands, cytosolic tyrosine kinases, heterocomplex formation or enhanced ligand expression. AT1R-EGFR crosstalk amplifies the signaling response and enhances the biological effects of angiotensin II. Downstream signaling cascades include ERK1/2 and p38 MAPK, PLCγ and STAT. AT1R-induced EGFR activation contributes to vascular remodeling and hypertrophy via e.g. smooth muscle cell proliferation, migration and extracellular matrix production. EGFR transactivation results in increased vessel wall thickness and reduced vascular compliance. AT1R and EGFR signaling pathways are also implicated the induction of vascular inflammation. Again, EGFR transactivation exacerbates the effects, leading to endothelial dysfunction that contributes to vascular inflammation, dysfunction and remodeling. Dysregulation of the AT1R-EGFR axis has been implicated in the pathogenesis of various cardiovascular diseases and inhibition or prevention of EGFR signaling can attenuate part of the detrimental impact of enhanced renin-angiotensin-system (RAAS) activity, highlighting the importance of EGFR for the adverse consequences of AT1R activation. In summary, EGFR plays a critical role in vascular AT1R action, enhancing signaling, promoting remodeling, contributing to inflammation, and participating in the pathogenesis of cardiovascular diseases. Understanding the interplay between AT1R and EGFR will foster the development of effective therapeutic strategies of RAAS-induced disorders.
Epidermal growth factor receptor and integrins meet redox signaling through P66shc and Rac1
2021, Cytokine
This review examines the concerted role of Epidermal Growth Factor Receptor (EGFR) and integrins in regulating Reactive oxygen species (ROS) production through different signaling pathways. ROS as such are not always deleterious to the cells but they also act as signaling molecules, that regulates numerous indespensible physiological fuctions of life. Many adaptor proteins, particularly Shc and Grb2, are involved in mediating the downstream signaling pathways stimulated by EGFR and integrins. Integrin-induced activation of EGFR and subsequent tyrosine phosphorylation of a class of acceptor sites on EGFR leads to alignment and tyrosine phosphorylation of Shc, PLCγ, the p85 subunit of PI-3 K, and Cbl, followed by activation of the downstream targets Erk and Akt/PKB. Functional interactions between these receptors result in the activation of Rac1 via these adaptor proteins, thereby leading to Reactive Oxygen Species. Both GF and integrin activation can produce oxidants independently, however synergistically there is increased ROS generation, suggesting a mutual cooperation between integrins and GFRs for redox signalling. The ROS produced further promotes feed-forward stimulation of redox signaling events such as MAPK activation and gene expression. This relationship has not been reviewed previously. The literature presented here can have multiple implications, ranging from looking at synergistic effects of integrin and EGFR mediated signaling mechanisms of different proteins to possible therapeutic interventions operated by these two receptors. Furthermore, such mutual redox regulation of crosstalk between EGFR and integrins not only add to the established models of pathological oxidative stress, but also can impart new avenues and opportunities for targeted antioxidant based therapeutics.
Transcriptional coactivator with PDZ-binding motif stimulates epidermal regeneration via induction of amphiregulin expression after ultraviolet damage
2020, Biochemical and Biophysical Research Communications
Ultraviolet (UV) irradiation induces the proliferation and differentiation of keratinocytes in the basal layer of the epidermis, which increases epidermal thickness in skin regeneration. However, the mechanism underlying this phenomenon is not yet known in detail. In this study, we aimed to demonstrate that the transcriptional coactivator with PDZ-binding motif (TAZ) stimulates epidermal regeneration by increasing keratinocyte proliferation. During epidermal regeneration, TAZ is localized in the nucleus of keratinocytes of the basal layer and stimulates epidermal growth factor receptor (EGFR) signaling. TAZ depletion in keratinocytes decreased EGFR signaling activation, which delays epidermal regeneration. Interestingly, TAZ stimulated the transcription of amphiregulin (AREG), a ligand of EGFR, through TEAD-mediated transcriptional activation. Together, these results show that TAZ stimulates EGFR signaling through AREG induction, suggesting that it plays an important role in epidermal regeneration.
A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts
2019, Journal of Ginseng Research
The efficacy of ginseng, the representative product of Korea, and its chemical effects have been well investigated. The ginsenoside RG3 has been reported to exhibit apoptotic, anticancer, and antidepressant-like effects.
In this report, the putative effect of RG3 on several cellular function including cell survival, differentiation, development and aging process were evaluated by monitoring each specific marker. Also, mitochondrial morphology and function were investigated in ultraviolet (UV)-irradiated normal human dermal fibroblast cells.
RG3 treatment increased the expression of extracellular matrix proteins, growth-associated immediate-early genes, and cell proliferation genes in UV-irradiated normal human dermal fibroblast cells. And, RG3 also resulted in enhanced expression of antioxidant proteins such as nuclear factor erythroid 2–related factor-2 and heme oxygenase-1. In addition, RG3 affects the morphology of UV-induced mitochondria and plays a role in protecting mitochondrial dysfunction.
RG3 restores mitochondrial adenosine triphosphate (ATP) and membrane potential via its antioxidant effects in skin cells damaged by UV irradiation, leading to an increase in proteins linked with the extracellular matrix, cell proliferation, and antioxidant activity.
BCKDK of BCAA Catabolism Cross-talking With the MAPK Pathway Promotes Tumorigenesis of Colorectal Cancer
2017, EBioMedicine
Branched-chain amino acids catabolism plays an important role in human cancers. Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, and the new global incidence is over 1.2 million cases. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) is a rate-limiting enzyme in branched-chain amino acids catabolism, which plays an important role in many serious human diseases. Here we investigated that abnormal branched-chain amino acids catabolism in colorectal cancer is a result of the disease process, with no role in disease initiation; BCKDK is widely expressed in colorectal cancer patients, and those patients that express higher levels of BCKDK have shorter survival times than those with lower levels; BCKDK promotes cell transformation or colorectal cancer ex vivo or in vivo. Mechanistically, BCKDK promotes colorectal cancer by enhancing the MAPK signaling pathway through direct MEK phosphorylation, rather than by branched-chain amino acids catabolism. And the process above could be inhibited by a BCKDK inhibitor, phenyl butyrate.
Redox regulation of FoxO transcription factors
2015, Redox Biology
Transcription factors of the forkhead box, class O (FoxO) family are important regulators of the cellular stress response and promote the cellular antioxidant defense. On one hand, FoxOs stimulate the transcription of genes coding for antioxidant proteins located in different subcellular compartments, such as in mitochondria (i.e. superoxide dismutase-2, peroxiredoxins 3 and 5) and peroxisomes (catalase), as well as for antioxidant proteins found extracellularly in plasma (e.g., selenoprotein P and ceruloplasmin). On the other hand, reactive oxygen species (ROS) as well as other stressful stimuli that elicit the formation of ROS, may modulate FoxO activity at multiple levels, including posttranslational modifications of FoxOs (such as phosphorylation and acetylation), interaction with coregulators, alterations in FoxO subcellular localization, protein synthesis and stability. Moreover, transcriptional and posttranscriptional control of the expression of genes coding for FoxOs is sensitive to ROS. Here, we review these aspects of FoxO biology focusing on redox regulation of FoxO signaling, and with emphasis on the interplay between ROS and FoxOs under various physiological and pathophysiological conditions. Of particular interest are the dual role played by FoxOs in cancer development and their key role in whole body nutrient homeostasis, modulating metabolic adaptations and/or disturbances in response to low vs. high nutrient intake. Examples discussed here include calorie restriction and starvation as well as adipogenesis, obesity and type 2 diabetes.

View all citing articles on Scopus

^‡: Present address: Medizinische Hochschule Hannover, Institut für Klinische Chemie, D-30623 Hannover, Federal Republic of Germany.

View full text

Cell

ArticleInvolvement of growth factor receptors in the mammalian UVC response

Abstract

J. Biol. Chem.

Cell

Cell

J. Biol. Chem.

Cell

Cell

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

Cell

Cell

J. Biol. Chem.

Biochem. Pharmacol.

Trends Biochem. Sci.

Neuron

Cell

Cell

Curr. Opin. Genet. Dev

J. Invest. Dermatol.

12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region

Mol. Cell. Biol.

Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor-induced mitogenesis by suramin

Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element

Oncogene

Rapid and preferential activation of the c-jun gene during the mammalian UV response

Mol. Cell. Biol.

NF-κB activation by ultraviolet light not dependent on a nuclear signal

Science

UVR induction of TGFα: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis

Carcinogenesis

Article
Involvement of growth factor receptors in the mammalian UVC response