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Mitogen-Activated Protein Kinases: New Insights for Old Cell Signaling Pathways

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 12459

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Special Issue Editors

Dr. Salvatore Papa

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Guest Editor

Leeds Institute of Medical Research at St. James’s, Faculty of Medicine and Health, University of Leeds, Leeds, UK
Interests: apoptosis; cancer; injury and repair; regeneration; kinase; signal transduction
Special Issues, Collections and Topics in MDPI journals

Dr. Concetta Bubici

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Guest Editor

Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The mitogen-activated protein kinase (MAPK) signaling pathway is a family of protein kinases that regulates many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is well established that mammals express three MAPK subfamilies: (a) the extracellular signal‐regulated kinases (ERKs); (b) the c‐Jun N‐terminal kinases/stress‐activated protein kinases (JNKs/SAPKs); and (c) the p38 MAPKs. Depending on distinct stimuli, each MAPK is activated by specific MAPKKs, which in turns can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signaling. Importantly, deregulated activation of these signaling pathways are becoming the focus of screening strategies probing for new therapeutic approaches to treat human diseases such as diabetes, neurodegenerative conditions, cardiovascular abnormalities, cancer, inflammation and liver disease.

Although these signaling pathways have been a subject of intensive research for more than two decades, only recent research focuses have greatly contributed to understand the biological activities and functions of each MAPK subfamilies in human diseases. This special issue aims to collect state-of-the-art primary research studies and review articles from diverse leading groups in the field to update our current understanding of the contributions of ERK, JNK and p38 MAPK to the development and control of specific human conditions. Written by international experts, this special issue may include research articles describing the regulatory mechanisms as well as the contribution of each MAPK subfamily to gene transcription and expression, metabolism, cell cycle regulation, immune responses and tumorigenesis therapeutic perspectives

Dr. Salvatore Papa
Dr. Concetta Bubici
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

JNK
ERK
p38
inflammatory responses
morphogenesis
cell proliferation
cell differentiation
cell survival
cell death
tissue regeneration
cancer
injury and repair
gene functions and genetics
gene transcription and expression
signaling networks and system biology
drugs and inhibitors
metabolism

Published Papers (4 papers)

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Research

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16 pages, 3173 KiB

Open AccessArticle

SB203580—A Potent p38 MAPK Inhibitor Reduces the Profibrotic Bronchial Fibroblasts Transition Associated with Asthma

by Milena Paw, Dawid Wnuk, Kinga Nit, Sylwia Bobis-Wozowicz, Rafał Szychowski, Alicja Ślusarczyk, Zbigniew Madeja and Marta Michalik

Int. J. Mol. Sci. 2021, 22(23), 12790; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312790 - 26 Nov 2021

Cited by 12 | Viewed by 2965

Abstract

Subepithelial fibrosis is a component of the remodeling observed in the bronchial wall of patients diagnosed with asthma. In this process, human bronchial fibroblasts (HBFs) drive the fibroblast-to-myofibroblast transition (FMT) in response to transforming growth factor-β₁ (TGF-β₁), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-β₁ also promote the activation of non-canonical signaling pathways which can affect the FMT. In this study we investigated the effect of p38 mitogen-activated protein kinase (MAPK) inhibition by SB203580 on the FMT potential of HBFs derived from asthmatic patients using immunocytofluorescence, real-time PCR and Western blotting methods. Our results demonstrate for the first time the strong effect of p38 MAPK inhibition on the TGF-β₁-induced FMT potential throughout the strong attenuation of myofibroblast-related markers: α-smooth muscle actin (α-SMA), collagen I, fibronectin and connexin 43 in HBFs. We suggest the pleiotropic mechanism of SB203580 on FMT impairment in HBF populations by the diminishing of TGF-β/Smad signaling activation and disturbances in the actin cytoskeleton architecture along with the maturation of focal adhesion sites. These observations justify future research on the role of p38 kinase in FMT efficiency and bronchial wall remodeling in asthma. Full article

(This article belongs to the Special Issue Mitogen-Activated Protein Kinases: New Insights for Old Cell Signaling Pathways)

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18 pages, 2086 KiB

Open AccessArticle

Bacteroides fragilis Enterotoxin Upregulates Matrix Metalloproteinase-7 Expression through MAPK and AP-1 Activation in Intestinal Epithelial Cells, Leading to Syndecan-2 Release

by Jong Ik Jeon, Keun Hwa Lee and Jung Mogg Kim

Int. J. Mol. Sci. 2021, 22(21), 11817; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111817 - 30 Oct 2021

Cited by 3 | Viewed by 1519

Abstract

Bacteroides fragilis enterotoxin (BFT) produced by enterotoxigenic B. fragilis (ETBF) causes colonic inflammation. BFT initially contacts intestinal epithelial cells (IECs) and affects the intestinal barrier. Although molecular components of the gut epithelial barrier such as metalloproteinase-7 (MMP-7) and syndecan-2 are known to be associated with inflammation, little has been reported about MMP-7 expression and syndecan-2 shedding in response to ETBF infection. This study explores the role of BFT in MMP-7 induction and syndecan-2 release in IECs. Stimulating IECs with BFT led to the induction of MMP-7 and the activation of transcription factors such as NF-κB and AP-1. MMP-7 upregulation was not affected by NF-κB, but it was related to AP-1 activation. In BFT-exposed IECs, syndecan-2 release was observed in a time- and concentration-dependent manner. MMP-7 suppression was associated with a reduction in syndecan-2 release. In addition, suppression of ERK, one of the mitogen-activated protein kinases (MAPKs), inhibited AP-1 activity and MMP-7 expression. Furthermore, the suppression of AP-1 and ERK activity was related to the attenuation of syndecan-2 release. These results suggest that a signaling cascade comprising ERK and AP-1 activation in IECs is involved in MMP-7 upregulation and syndecan-2 release during exposure to BFT. Full article

(This article belongs to the Special Issue Mitogen-Activated Protein Kinases: New Insights for Old Cell Signaling Pathways)

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16 pages, 3088 KiB

Open AccessArticle

Involvement of cAMP-Dependent Protein Kinase in the Nucleus Accumbens in Cocaine Versus Social Interaction Reward

by Inês M. Amaral, Cristina Lemos, Isabella Cera, Georg Dechant, Alex Hofer and Rana El Rawas

Int. J. Mol. Sci. 2021, 22(1), 345; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010345 - 31 Dec 2020

Cited by 7 | Viewed by 2225

Abstract

Evidence suggests that PKA activity in the nucleus accumbens (NAc) plays an essential role in reward-related learning. In this study, we investigated whether PKA is differentially involved in the expression of learning produced by either natural reinforcers or psychostimulants. For that purpose, we inhibited PKA through a bilateral infusion of Rp-cAMPS, a specific PKA inhibitor, directly into the NAc. The effects of PKA inhibition in the NAc on the expression of concurrent conditioned place preference (CPP) for cocaine (drug) and social interaction (natural reward) in rats were evaluated. We found that PKA inhibition increased the expression of cocaine preference. This effect was not due to altered stress levels or decreased social reward. PKA inhibition did not affect the expression of natural reward as intra-NAc Rp-cAMPS infusion did not affect expression of social preference. When rats were trained to express cocaine or social interaction CPP and tested for eventual persisting preference 7 and 14 days after CPP expression, cocaine preference was persistent, but social preference was abolished after the first test. These results suggest that PKA in the NAc is involved in drug reward learning that might lead to addiction and that only drug, but not natural, reward is persistent. Full article

(This article belongs to the Special Issue Mitogen-Activated Protein Kinases: New Insights for Old Cell Signaling Pathways)

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Review

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14 pages, 2082 KiB

Open AccessReview

Pseudophosphatases as Regulators of MAPK Signaling

by Emma Marie Wilber Hepworth and Shantá D. Hinton

Int. J. Mol. Sci. 2021, 22(22), 12595; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212595 - 22 Nov 2021

Cited by 29 | Viewed by 5091

Abstract

Mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved regulators of eukaryotic cell function. These enzymes regulate many biological processes, including the cell cycle, apoptosis, differentiation, protein biosynthesis, and oncogenesis; therefore, tight control of the activity of MAPK is critical. Kinases and phosphatases are well established as MAPK activators and inhibitors, respectively. Kinases phosphorylate MAPKs, initiating and controlling the amplitude of the activation. In contrast, MAPK phosphatases (MKPs) dephosphorylate MAPKs, downregulating and controlling the duration of the signal. In addition, within the past decade, pseudoenzymes of these two families, pseudokinases and pseudophosphatases, have emerged as bona fide signaling regulators. This review discusses the role of pseudophosphatases in MAPK signaling, highlighting the function of phosphoserine/threonine/tyrosine-interacting protein (STYX) and TAK1-binding protein (TAB 1) in regulating MAPKs. Finally, a new paradigm is considered for this well-studied cellular pathway, and signal transduction pathways in general. Full article

(This article belongs to the Special Issue Mitogen-Activated Protein Kinases: New Insights for Old Cell Signaling Pathways)

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