<b>Regulation of human mitogen‐activated protein kinase 15 (extracellular signal‐regulated kinase 7/8) and its functions: A recent update</b>

Lau, Andy T. Y.; Xu, Yan‐Ming

doi:10.1002/jcp.27053

Cited by 32 publications

(31 citation statements)

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“…The ERK pathway comprises several proteins that belongs to the family of mitogen-activated protein kinases (MAPK). These regulate diverse physiological and cellular processes, such as gene expression, cell division, survival, apoptosis, differentiation, and motility [15,16]. In metastatic processes, the MAPKs regulate EMT, invasion, angiogenesis, and resistance to therapy [7].…”

Section: Extracellular-signal Regulated Kinase: Structure and Funcmentioning

confidence: 99%

“…Within the conventional MAPKs, the following subfamilies are categorized: ERKs, c-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) and p38, and ERK1/2 and ERK5. ERK3/4 and ERK7/8 are atypical MAPKs [15,17]. Several members of the ERK subfamily participate in regulation of growth, differentiation, survival, and cell motility [18].…”

Section: Extracellular-signal Regulated Kinase: Structure and Funcmentioning

confidence: 99%

“…Six members of the ERK subfamily have been identified (Table 1, Figure 1): ERK1/2, 3/4, 5 and 7/8. Of these, only ERK3/4 do not present isoforms [15]. ERK1/2 are the two most studied kinases and the main regulators of the MAPK/ERK signal pathway [15].…”

Section: Extracellular-signal Regulated Kinase: Structure and Funcmentioning

confidence: 99%

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Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer

Olea-Flores

Zuñiga-Eulogio

Mendoza-Catalán

et al. 2019

IJMS

117

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Epithelial–mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4/7/8) members. These kinases are overexpressed and hyperactive in various types of cancer. They regulate diverse cellular processes such as proliferation, migration, metastasis, resistance to chemotherapy, and EMT. In this context, in vitro and in vivo assays, as well as studies in human patients, have shown that ERK favors the expression, function, and subcellular relocalization of various proteins that regulate EMT, thus promoting tumor progression. In this review, we discuss the mechanistic roles of the ERK subfamily members in EMT and tumor progression in diverse biological systems.

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Section: Extracellular-signal Regulated Kinase: Structure and Funcmentioning

confidence: 99%

Section: Extracellular-signal Regulated Kinase: Structure and Funcmentioning

confidence: 99%

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Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer

Olea-Flores

Zuñiga-Eulogio

Mendoza-Catalán

et al. 2019

IJMS

117

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“…MAPK15 is the most recently identified member of the MAPK family (16), and it is widely accepted to be upregulated in a variety of cancer types. Studies have shown that unlike other members of the MAPK family, the phosphorylation of MAPK15 is mainly self-phosphorylation, so its total protein level is positively correlated with the phosphorylation level (17,18). Additionally, the overexpression of MAPK15 promoted gastric cancer cell proliferation by stabilizing the expression of c-Jun (19).…”

Section: Metastasis-associated Gene Mapk15 Promotes the Migration Andmentioning

confidence: 99%

Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway

Yang

Zeng

et al. 2020

Oncol Lett

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Osteosarcoma (OS) is the most common and destructive primary bone malignancy to affect children and adolescents. Metastases remain the primary cause of death in patients with OS. In the present study, weight gene co-expressed network analysis (WGCNA) and differentially-expressed gene analysis were used to identify key genes associated with the metastasis of OS. Reverse transcription-quantitative PCR and immunohistochemical staining were then used to detect the expression levels of these key genes in OS tissues, and to determine the hub genes of interest. Wound-healing and transwell assays, in addition to a lung metastasis model, were used to detect the effects of the hub genes on OS cell proliferation and metastasis in vitro and in vivo. Using WGCNA and differential expression analysis, deleted in lung and esophageal cancer protein 1 (DLEC1), Forkhead box J1 (FOXJ1) and mitogen-activated protein kinase 15 (MAPK15) were predicted to be key metastasis-associated genes, and highly expressed in metastatic OS tissues; among them, the protein and mRNA expression levels of MAPK15 were most significantly increased in our OS tissues from patients who exhibited metastases at diagnosis, and thus MAPK15 was determined to be a metastasis-associated hub gene to further study. Furthermore, inhibiting MAPK15 expression significantly decreased OS cell metastasis in vitro and in vivo, as well as suppressing c-Jun/matrix metalloproteinase (MMP)-associated pathways. Overexpression of MAPK15 activated the c-Jun/MMPs pathway and promoted OS cell metastasis, while inhibition of c-Jun blocked this effect. Taken together, MAPK15 was indicated to be an OS metastasis-associated gene, and was confirmed to promote the migration and invasion of OS cells via the c-Jun/MMP pathway. MAPK15 may therefore be an effective target for the treatment of OS.

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“…Accumulating evidences have shown that atypical MAPKs play critical roles in the development of tissues and participate in various diseases [8][9][10]. MAPK4, alias ERK4 or p63 MAPK, is the member of atypical MAPKs and closely related to MAPK6 with 73% amino acid identity in the kinase domain [11].…”

Section: Introductionmentioning

confidence: 99%

Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

Mao

Zhou

Chen

et al. 2020

Preprint

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Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Regulation of human mitogen‐activated protein kinase 15 (extracellular signal‐regulated kinase 7/8) and its functions: A recent update

Cited by 32 publications

References 50 publications

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer

Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway

Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

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