scholarly journals MAPK Activated Protein Kinase 3 Is a Prognostic-Related Biomarker and Associated With Immune Infiltrates in Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Ren ◽  
Jinmin Sun ◽  
Mengwei Li ◽  
Zifan Zhang ◽  
Dejun Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Immune Responses ◽  
Chemokine Receptors ◽  
Cellular Responses ◽  
Primary Brain Tumor ◽  
The Novel ◽  
Promising Target ◽  
Tumor Progress ◽  
Bioinformatic Approaches

Glioma is the most common primary brain tumor that causes significant morbidity and mortality. MAPK activated protein kinase 3 (MAPKAPK3/MK3) is a serine/threonine protein kinase regulating various cellular responses and gene expression. However, the role of MK3 in tumor progress, prognosis, and immunity for glioma remains unclear. Here, we determined the expression and prognostic values of MK3. We further analyzed the correlation of MK3 expression with immune infiltrations by using the biochemical methods and bioinformatic approaches with available databases. We find that MK3 is aberrantly upregulated in glioma. In addition, the higher MK3 expression is closely linked to the poor clinicopathologic features of glioma patients. Importantly, MK3 expression is negatively correlated with the prognosis of patients with glioma. Mechanistically, we demonstrated that the correlated genes of MK3 were mainly enriched in pathways that regulate tumor immune responses. The MK3 level was significantly associated with tumor-infiltrating immune cells and positively correlated with the majority of tumor immunoinhibitors, chemokines, and chemokine receptors in glioma. Thus, these findings suggest the novel prognostic roles of MK3 and define MK3 as a promising target for glioma immunotherapy.

scholarly journals Targeting Protein Kinase C in Glioblastoma Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 381
Author(s):  
Noelia Geribaldi-Doldán ◽  
Irati Hervás-Corpión ◽  
Ricardo Gómez-Oliva ◽  
Samuel Domínguez-García ◽  
Félix A. Ruiz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Combined Treatment ◽  
Primary Brain Tumor ◽  
Kinase C ◽  
Pkc Isozymes ◽  
New Generation ◽  
Effective Drugs

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.

scholarly journals Activation of a Mitogen-Activated Protein Kinase Hog1 by DNA Damaging Agent Methyl Methanesulfonate in Yeast

2020 ◽  
Vol 7 ◽  
Author(s):  
Shan Huang ◽  
David Zhang ◽  
Fangli Weng ◽  
Yuqi Wang
Keyword(s):  
Protein Kinase ◽  
Cellular Responses ◽  
Mitogen Activated Protein Kinase ◽  
Yeast Cells ◽  
Methyl Methanesulfonate ◽  
Regulate Gene Expression ◽  
Dna Damaging Agents ◽  
Mitogen Activated Protein ◽  
Regulate Gene

Hog1 is a mitogen-activated protein kinase in yeast that primarily regulates cellular responses to hyperosmolarity stress. In this study, we have examined the potential involvement of Hog1 in mediating cellular responses to DNA damaging agents. We find that treatment of yeast cells with DNA damaging agent methyl methanesulfonate (MMS) induces a marked and prolonged Hog1 activation. Distinct from stressors such as arsenite that activates Hog1 via inhibiting its phosphatases, activation of Hog1 by MMS is phosphatase-independent. Instead, MMS impairs a critical phosphor-relay process that normally keeps Hog1 in an inactive state. Functionally, MMS-activated Hog1 is not translocated to the nucleus to regulate gene expression but rather stays in the cytoplasm and regulates MMS-induced autophagy and cell adaptation to MMS stress. These findings reveal a new role of Hog1 in regulating MMS-induced cellular stress.

scholarly journals SARS-CoV-2 may regulate cellular responses through depletion of specific host miRNAs

2020 ◽  
Vol 319 (3) ◽  
pp. L444-L455 ◽  
Author(s):  
Rafal Bartoszewski ◽  
Michal Dabrowski ◽  
Bogdan Jakiela ◽  
Sadis Matalon ◽  
Kevin S. Harrod ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mirna Target ◽  
Cellular Responses ◽  
Specific Host ◽  
Global Pandemic ◽  
Target Sites ◽  
Bioinformatic Approaches ◽  
Mirna Sponges ◽  
Human Coronaviruses ◽  
Respiratory Coronavirus

Cold viruses have generally been considered fairly innocuous until the appearance of the severe acute respiratory coronavirus 2 (SARS-CoV-2) in 2019, which caused the coronavirus disease 2019 (COVID-19) global pandemic. Two previous viruses foreshadowed that a coronavirus could potentially have devastating consequences in 2002 [severe acute respiratory coronavirus (SARS-CoV)] and in 2012 [Middle East respiratory syndrome coronavirus (MERS-CoV)]. The question that arises is why these viruses are so different from the relatively harmless cold viruses. On the basis of an analysis of the current literature and using bioinformatic approaches, we examined the potential human miRNA interactions with the SARS-CoV-2’s genome and compared the miRNA target sites in seven coronavirus genomes that include SARS-CoV-2, MERS-CoV, SARS-CoV, and four nonpathogenic coronaviruses. Here, we discuss the possibility that pathogenic human coronaviruses, including SARS-CoV-2, could modulate host miRNA levels by acting as miRNA sponges to facilitate viral replication and/or to avoid immune responses.

scholarly journals Protein kinase C mechanisms that contribute to cardiac remodelling

2016 ◽  
Vol 130 (17) ◽  
pp. 1499-1510 ◽  
Author(s):  
Alexandra C. Newton ◽  
Corina E. Antal ◽  
Susan F. Steinberg
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Cardiac Contractility ◽  
Cellular Responses ◽  
Growth Responses ◽  
Kinase C ◽  
Wide Range ◽  
Clinical Disorders

Protein phosphorylation is a highly-regulated and reversible process that is precisely controlled by the actions of protein kinases and protein phosphatases. Factors that tip the balance of protein phosphorylation lead to changes in a wide range of cellular responses, including cell proliferation, differentiation and survival. The protein kinase C (PKC) family of serine/threonine kinases sits at nodal points in many signal transduction pathways; PKC enzymes have been the focus of considerable attention since they contribute to both normal physiological responses as well as maladaptive pathological responses that drive a wide range of clinical disorders. This review provides a background on the mechanisms that regulate individual PKC isoenzymes followed by a discussion of recent insights into their role in the pathogenesis of diseases such as cancer. We then provide an overview on the role of individual PKC isoenzymes in the regulation of cardiac contractility and pathophysiological growth responses, with a focus on the PKC-dependent mechanisms that regulate pump function and/or contribute to the pathogenesis of heart failure.

Protein kinase C: a regulator of cytoskeleton remodelling and T-cell migration

2014 ◽  
Vol 42 (6) ◽  
pp. 1490-1497 ◽  
Author(s):  
Aideen Long ◽  
Michael Freeley
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
Cell Migration ◽  
T Cell ◽  
Protein Kinase ◽  
Immune Responses ◽  
Chemokine Receptors ◽  
T Cell Subsets ◽  
T Cell Migration ◽  
Kinase C

Protein kinase C (PKC) is a family of ten serine/threonine kinases that have diverse roles in the signalling pathways regulating cellular proliferation, differentiation, apoptosis and immune responses. Elucidating roles for individual PKC isoforms in the immune responses of T-cells have long been a challenging prospect, because these cells are known to express nine of these isoforms. A variety of approaches including the use of knockout mice, overexpression of kinase-inactive mutants, cell-permeable peptides, pharmacological inhibitors and siRNAs have shown that PKCs regulate the production of inflammatory cytokines and the cytotoxic responses of various T-cell subsets. Central to the T-cell immune response is a requirement to migrate to various organs and tissues in search of pathogens and micro-organisms. T-cell migration is guided by specific sets of chemokines and integrin ligands that activate their cognate chemokine receptors and integrins on T-cells, resulting in remodelling of the cytoskeleton and the dynamic protrusive/contractile forces necessary for cell adhesion and motility. In the present article, we review the role of PKC in T-cell migration, with an emphasis on studies that have defined their roles in cytoskeletal remodelling, cell polarity and intracellular trafficking downstream of chemokine receptors and integrins.

scholarly journals Long noncoding RNAAVANpromotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

2019 ◽  
Author(s):  
Chengcai Lai ◽  
Lihui Liu ◽  
Qinghua Liu ◽  
Sijie Cheng ◽  
Keyu Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Virus Production ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Forkhead Box ◽  
Innate Immune Signaling ◽  
Promising Target ◽  
Antiviral Innate Immunity

AbstractAccumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVANpositively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVANdirectly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVANas a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.

The role of chemokines and their receptors during protist parasite infections

Parasitology ◽  
2016 ◽  
Vol 143 (14) ◽  
pp. 1890-1901 ◽  
Author(s):  
FIONA M. MENZIES ◽  
DAVID MACPHAIL ◽  
FIONA L. HENRIQUEZ
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Chemokine Receptors ◽  
Drug Targeting ◽  
Scientific Literature ◽  
Parasite Survival ◽  
Recent Developments ◽  
Parasite Infections ◽  
Eukaryotic Organisms

SUMMARYProtists are a diverse collection of eukaryotic organisms that account for a significant global infection burden. Often, the immune responses mounted against these parasites cause excessive inflammation and therefore pathology in the host. Elucidating the mechanisms of both protective and harmful immune responses is complex, and often relies of the use of animal models. In any immune response, leucocyte trafficking to the site of infection, or inflammation, is paramount, and this involves the production of chemokines, small chemotactic cytokines of approximately 8–10 kDa in size, which bind to specific chemokine receptors to induce leucocyte movement. Herein, the scientific literature investigating the role of chemokines in the propagation of immune responses against key protist infections will be reviewed, focussing onPlasmodiumspecies,Toxoplasma gondii, Leishmaniaspecies andCryptosporidiumspecies. Interestingly, many studies find that chemokines can in fact, promote parasite survival in the host, by drawing in leucocytes for spread and further replication. Recent developments in drug targeting against chemokine receptors highlights the need for further understanding of the role played by these proteins and their receptors in many different diseases.

scholarly journals Role of Protein Kinase C (PKC) in Short- and Long-Term Cellular Responses

1988 ◽  
Vol 12 ◽  
pp. 73-79 ◽  
Author(s):  
Doriano Fabbro ◽  
Nachman Mazurek ◽  
Christoph Borner ◽  
Jean-François Conscience ◽  
Paul Erne
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Responses ◽  
Kinase C ◽  
Short And Long Term
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