scholarly journals Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies

2007 ◽  
Vol 405 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Joseph Friedman ◽  
Sarah Kraus ◽  
Yirmi Hauptman ◽  
Yoni Schiff ◽  
Rony Seger
Keyword(s):  
Mobile Phone ◽  
Electromagnetic Fields ◽  
Mobile Phones ◽  
Egf Receptor ◽  
Nadh Oxidase ◽  
Mitogen Activated Protein Kinase ◽  
Heparin Binding ◽  
Cellular Processes ◽  
Mapk Cascades ◽  
Mitogen Activated Protein

The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes.

The Nuclear Translocation of Mitogen-Activated Protein Kinases: Molecular Mechanisms and Use as Novel Therapeutic Target

2018 ◽  
Vol 108 (2) ◽  
pp. 121-131 ◽  
Author(s):  
Karen Flores ◽  
Suresh Singh Yadav ◽  
Arieh A. Katz ◽  
Rony Seger
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Processes ◽  
Development Of Resistance ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Importin Α ◽  
Cancer And Inflammation

The mitogen-activated protein kinase (MAPK) cascades are central signaling pathways that play a central role in the regulation of most stimulated cellular processes including proliferation, differentiation, stress response and apoptosis. Currently 4 such cascades are known, each termed by its downstream MAPK components: the extracellular signal-regulated kinase 1/2 (ERK1/2), cJun-N-terminal kinase (JNK), p38 and ERK5. One of the hallmarks of these cascades is the stimulated nuclear translocation of their MAPK components using distinct mechanisms. ERK1/2 are shuttled into the nucleus by importin7, JNK and p38 by a dimer of importin3 with either importin9 or importin7, and ERK5 by importin-α/β. Dysregulation of these cascades often results in diseases, including cancer and inflammation, as well as developmental and neurological disorders. Much effort has been invested over the years in developing inhibitors to the MAPK cascades to combat these diseases. Although some inhibitors are already in clinical use or clinical trials, their effects are hampered by development of resistance or adverse side-effects. Recently, our group developed 2 myristoylated peptides: EPE peptide, which inhibits the interaction of ERK1/2 with importin7, and PERY peptide, which prevents JNK/p38 interaction with either importin7 or importin9. These peptides block the nuclear translocation of their corresponding kinases, resulting in prevention of several cancers, while the PERY peptide also inhibits inflammation-induced diseases. These peptides provide a proof of concept for the use of the nuclear translocation of MAPKs as therapeutic targets for cancer and/or inflammation.

scholarly journals Alternative Splicing of MAPKs in the Regulation of Signaling Specificity

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3466
Author(s):  
Galia Maik-Rachline ◽  
Inbal Wortzel ◽  
Rony Seger
Keyword(s):  
Cell Fate ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Specificity ◽  
Cellular Processes ◽  
Extracellular Signals ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Extracellular Stimuli ◽  
Alternatively Spliced

The mitogen-activated protein kinase (MAPK) cascades transmit signals from extracellular stimuli to a variety of distinct cellular processes. The MAPKKs in each cascade specifically phosphorylate and activate their cognate MAPKs, indicating that this step funnels various signals into a seemingly linear pathway. Still, the effects of these cascades vary significantly, depending on the identity of the extracellular signals, which gives rise to proper outcomes. Therefore, it is clear that the specificity of the signals transmitted through the cascades is tightly regulated in order to secure the desired cell fate. Indeed, many regulatory components or processes that extend the specificity of the cascades have been identified. Here, we focus on a less discussed mechanism, that is, the role of distinct components in each tier of the cascade in extending the signaling specificity. We cover the role of distinct genes, and the alternatively spliced isoforms of MAPKKs and MAPKs, in the signaling specificity. The alternatively spliced MEK1b and ERK1c, which form an independent signaling route, are used as the main example. Unlike MEK1/2 and ERK1/2, this route’s functions are limited, including mainly the regulation of mitotic Golgi fragmentation. The unique roles of the alternatively spliced isoforms indicate that these components play an essential role in determining the proper cell fate in response to distinct stimulations.

Arabidopsis MAPKs: a complex signalling network involved in multiple biological processes

2008 ◽  
Vol 413 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Jean Colcombet ◽  
Heribert Hirt
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Model ◽  
Global Scale ◽  
Mitogen Activated Protein Kinase ◽  
Model Organisms ◽  
Cellular Processes ◽  
Mapk Cascades ◽  
Signal Transduction Networks ◽  
Future Challenges ◽  
Mitogen Activated Protein

Many changes in environmental conditions and hormones are mediated by MAPK (mitogen-activated protein kinase) cascades in all eukaryotes, including plants. Studies of MAPK pathways in genetic model organisms are especially informative in revealing the molecular mechanisms by means of which MAPK cascades are controlled and modulate cellular processes. The present review highlights recent insights into MAPK-based signalling in Arabidopsis thaliana (thale cress), revealing the complexity and future challenges to understanding signal-transduction networks on a global scale.

scholarly journals Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle

2004 ◽  
Vol 63 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Yun Chau Long ◽  
Ulrika Widegren ◽  
Juleen R. Zierath
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Exercise Induced ◽  
Response To Exercise

Exercise training improves glucose homeostasis through enhanced insulin sensitivity in skeletal muscle. Muscle contraction through physical exercise is a physiological stimulus that elicits multiple biochemical and biophysical responses and therefore requires an appropriate control network. Mitogen-activated protein kinase (MAPK) signalling pathways constitute a network of phosphorylation cascades that link cellular stress to changes in transcriptional activity. MAPK cascades are divided into four major subfamilies, including extracellular signal-regulated kinases 1 and 2, p38 MAPK, c-Jun NH2-terminal kinase and extracellular signal-regulated kinase 5. The present review will present the current understanding of parallel MAPK signalling in human skeletal muscle in response to exercise and muscle contraction, with an emphasis on identifying potential signalling mechanisms responsible for changes in gene expression.

scholarly journals EGF stimulates gastrin promoter through activation of Sp1 kinase activity

2000 ◽  
Vol 278 (4) ◽  
pp. C697-C708 ◽  
Author(s):  
Sergey Chupreta ◽  
Ming Du ◽  
Andrea Todisco ◽  
Juanita L. Merchant
Keyword(s):  
Kinase Activity ◽  
Egf Receptor ◽  
Solid Phase ◽  
Receptor Activation ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Assay ◽  
Ags Cells ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Epidermal growth factor (EGF) receptor activation stimulates gastrin gene expression through a GC-rich element called gastrin EGF response element (gERE). This element is bound by Sp1 family members and is a target of the ras-extracellular signal-regulated kinase (Erk) signal transduction cascade. This raised the possibility that Sp1 may be phosphorylated by kinases of this signaling pathway. Erk is capable of phosphorylating other mitogen-inducible transcription factors, e.g., Elk and Sap, suggesting that Erk may also mediate EGF-dependent phosphorylation of Sp1. This possibility was tested by studying Sp1-dependent kinase activity in extracts prepared from EGF-activated AGS cells by use of solid-phase kinase assays and immunoprecipitation of metabolically labeled Sp1. The results revealed that Sp1 kinase activity (like gastrin promoter activation) is inhibited by PD-98059 and, therefore, is dependent on mitogen-activated protein kinase kinase 1 (Mek 1). However, EGF-dependent activation of endogenous Erk did not account for most of the Sp1 kinase activity, since Erk and additional Sp1 kinase activity analyzed in a solid-phase kinase assay eluted from an ion-exchange column in different fractions. Phosphoamino acid analysis of in vivo radiolabeled Sp1 demonstrated that the kinase phosphorylates Sp1 on Ser and Thr in response to EGF. Therefore, most EGF-stimulated Sp1 kinase activity is Mek 1 dependent and distinct from Erk.

C-terminal heparin-binding domain of fibronectin regulates integrin-mediated cell spreading but not the activation of mitogen-activated protein kinase

2001 ◽  
Vol 360 (1) ◽  
pp. 239-245 ◽  
Author(s):  
Jungyean KIM ◽  
Innoc HAN ◽  
Yeonhee KIM ◽  
Seungin KIM ◽  
Eok-Soo OH
Keyword(s):  
Cell Spreading ◽  
Binding Domain ◽  
Mitogen Activated Protein Kinase ◽  
Heparin Binding ◽  
Cell Binding ◽  
Rat Embryo ◽  
Mapk Activation ◽  
Mitogen Activated Protein ◽  
Heparin Binding Domain ◽  
Cell Binding Domain

Fibronectin (FN) stimulates multiple signalling events including mitogen-activated protein kinase (MAPK) activation. During cell spreading, both the cell-binding domain and the C-terminal heparin-binding domain (HepII) of FN co-operatively regulate cytoskeleton organization. However, in comparison with the large number of studies on the functions of cell-binding domain, there is little information about the role of HepII. We therefore investigated the effect of HepII on integrin-mediated cell spreading and adhesion on FN and MAPK activation. In contrast with cells on FN substrates, rat embryo fibroblasts on FN120, which lacks HepII, were less spread, had weaker adhesion to FN and failed to form focal adhesions and actin stress fibres. Phosphotyrosine was present in the focal contacts of rat embryo fibroblasts on FN within 30min but was absent from cells on FN120. Overall, tyrosine phosphorylation was much less in cell lysates from cells on FN120, with decreased phosphorylation of focal adhesion kinase (‘pp125FAK’) on tyrosine-397, implying additional regulation of tyrosine phosphorylation by HepII. Nevertheless, adhesion-mediated MAPK activity was similar in cells on FN and on FN120. Furthermore, cells spread on FN and on FN120 substrates showed similar MAPK activation in response to treatment with epidermal growth factor and with platelet-derived growth factor. Consistently, overexpression of syndecan-4, which binds to HepII, enhanced cell spreading and adhesion on FN but did not affect integrin-mediated MAPK activation. We therefore conclude that both HepII and syndecan-4 regulate integrin-mediated cell spreading but not MAPK activation.

scholarly journals Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 707-714 ◽  
Author(s):  
Qi En Yang ◽  
Mariana I Giassetti ◽  
Alan D Ealy
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Trophoblast Cells ◽  
Migratory Activity ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Cattle And Sheep

Fibroblast growth factors (FGFs) 2 and FGF10 are uterine- and conceptus-derived factors that mediate trophoblast activities in cattle and sheep. To extend our understanding of how FGFs may control peri-implantation development in ruminants, we determined whether FGF2 and FGF10 impact trophoblast cell migration. Transwell inserts containing 8 μm pores were used to examine whether FGF2 or FGF10 supplementation increased oTr1 cell migration. Supplementation with 0.5 ng/ml FGF2 or FGF10 did not affect oTr1 cell migration number, but exposure to 5 or 50 ng/ml FGF2 or FGF10 increased (P<0.05) oTr1 cell migration when compared with controls. The involvement of specific MAP kinase (MAPK) cascades in mediating this FGF response was examined by using pharmacological inhibitors of specific MAPKs. Western blot analysis indicated that FGF2 and FGF10 increased phosphorylation status of MAPKs 1, 3, 8, 9, and 14. Exposure to specific inhibitors blocked FGF induction of each MAPK. Exposure to inhibitors before supplementation with FGF2 or FGF10 prevented FGF induction of cell migration, indicating that each of these signaling molecules was required for FGF effects. A final series of studies examined whether FGF2 and FGF10 also mediated the migration of a bovine trophoblast line (CT1 cell). Increases in migration were detected in each cell line by supplementing 5 or 50 ng/ml FGF2 or FGF10 (P<0.05). In summary, FGF2 and FGF10 regulate migratory activity of ovine trophoblast cells through MAPK-dependent pathways. These outcomes provide further evidence that FGFs function as mediators of peri-implantation conceptus development in cattle and sheep.

scholarly journals Genome-wide identification of MAPKKK genes and their response to phytoplasma stress in Chinese jujube (Ziziphus jujuba Mill.)

2019 ◽  
Author(s):  
ZhiGuo Liu ◽  
Lixin Wang ◽  
Chaoling Xue ◽  
Yuetong Chu ◽  
Weilin Gao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Expression Profiles ◽  
Duplication Event ◽  
Kinase Domain ◽  
Mitogen Activated Protein Kinase ◽  
Chinese Jujube ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Phytoplasma Infection ◽  
Gene Structures

Abstract Backgrounds Mitogen activated protein kinase (MAPK) cascades play vital roles in signal transduction in response to various biotic and abiotic stresses. In the previous study we have identified 10 ZjMAPKs and 5 ZjMAPKKs in Chinese jujube genome and found some crucial members of ZjMAPKs and ZjMAPKKs might function importantly in the process of phytoplasma infection. But how these ZjMAPKKs were modulated by ZjMAPKKKs during this process is still elusive and little information is known about the MAPKKKs in Chinese jujube. Results In the current study, 56 ZjMAPKKKs were identified in the jujube genome and all of them contain the key S-TKc (serine/threonine protein kinase) domain which distributed in all 12 chromosomes. Phylogenetic analysis showed that these ZjMAPKKKs could be classified into two subfamilies, of which 41 belonged to Raf, and 15 to MEKK subfamily. In addition, the ZjMAPKKKs in each subfamily share the same conserved motifs and gene structures, one pair of ZjMAPKKKs (15/16) was the only tandem duplication event on Chromosome 5. Furthermore, the expression profiles of these MAPKKKs in response to phytoplasma disease were investigated by qPCR. In the three main infected tissues (witches’ broom leaves, phyllody leaves, apparent normal leaves), the ZjMAPKKK26 and 45 were significantly up regulated and the ZjMAPKKK3, 43 and 50 were down regulated. While the ZjMAPKKK4, 10, 25 and 44 were significant highly induced in the sterile cultivated tissues infected by phytoplasma, and the ZjMAPKKK7, 30, 35, 37, 40, 41, 43 and 46 were significantly down regulated. Conclusions The identification and classification analysis of ZjMAPKKKs was firstly reported and some key individual ZjMAPKKKs genes might play essential roles in response to phytoplasma infection. This could provide initial understanding for the mechanism that how the ZjMAPKKKs were involved in jujube - phytoplasma infection.

Leptin is involved in acrosome reaction by facilitating activation of MAPK cascades in the Chinese mitten crab, Eriocheir sinensis

2020 ◽  
Vol 70 (1) ◽  
pp. 81-95
Author(s):  
Qing Li ◽  
Haitao Zhao ◽  
Lin He ◽  
Hongdan Yang ◽  
Qun Wang
Keyword(s):  
Acrosome Reaction ◽  
Calcium Ionophore ◽  
Eriocheir Sinensis ◽  
Calcium Ionophore A23187 ◽  
Mitogen Activated Protein Kinase ◽  
Ionophore A23187 ◽  
Mapk Cascades ◽  
Mitten Crab ◽  
Mitogen Activated Protein

Abstract The role of leptin has been documented in several studies, including activated threonine phosphorylation of extracellular signal-regulated kinase (ERK1/2) in the reproduction of rodents and humans. Our previous studies have demonstrated that mitogen-activated protein kinase (MAPK) cascades ERK, P38, and c-Jun N-terminal kinase (JNK) are involved in the spermatogenesis and acrosome reaction of Eriocheir sinensis. Therefore, the aim of this study was to investigate the expression of leptin and its receptor (LepR), and the effect of leptin on MAPK cascades during calcium ionophore A23187-induced spermatozoa acrosome reaction in crabs. Successful western blotting revealed a 16 kDa band for leptin, and 120 kDa and 90 kDa bands for the obese receptor (LepR), respectively, in the tested male reproductive tissues. Both leptin and LepR were localized at the pro-acrosomal vesicle and apical cap (AC) of spermatids, suggesting their role in the subsequent acrosome reaction. Moreover, acrosome reaction can be enhanced by leptin, and this effect decreased due to the anti-LepR antibody. Afterwards, we investigated the effects of leptin on MAPK cascades. The results showed that leptin mainly activated the phosphorylation of ERK, P38 and JNK proteins in the apical cap during the acrosome reaction in crab spermatozoa. This study addresses the role of leptin on spermatozoa, and suggests that leptin may induce molecular changes associated with spermatozoa during acrosome reaction.

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