MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway

Perry, Charles H.; Mullins, Nathan A.; Sweileh, Razan B.A.; Shendy, Noha A.M.; Roberto, Patrick A.; Broadhurst, Amber L.; Nelson, Hannah A.; Miranda-Carboni, Gustavo A.; Abell, Amy N.

doi:10.1016/j.jbc.2022.102310

Cited by 4 publications

(3 citation statements)

References 87 publications

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“…Consistent with previous studies, our findings demonstrated that MAP3K4 knockdown greatly decreased LDs formation by reducing JNK activation and subsequent cPLA2 phosphorylation at Ser-505 [ 49 , 57 ]. In addition, due to MAP3K4 control of the insulin-like growth factor 1 receptor, stem cells lacking MAP3K4 kinase activity are less sensitive to insulin stimulation [ 65 ]. This offers fresh insight for further research to investigate the function of MAP3K4 in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease

Bin

Chen

et al. 2022

J Transl Med

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Background Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder with abnormal lipid metabolism. The present study was to identify regulatory genes related to lipid droplets (LDs) abnormal accumulation in NAFLD. Methods transcriptomic analysis and bioinformatics analysis (GEO database) were used to identify potential genes in abnormal lipid metabolism of NAFLD. A candidate gene MAP3K4 expression were detected by immunohistochemistry staining in NAFLD and controls. RNA interference and immunoblotting were used to verify the roles of MAP3K4 in the formation of hepatic LDs. Results A total of 134 candidate genes were screened, including 44 up-regulated genes and 90 down-regulated genes. 29 genes in the protein–protein interaction (PPI) were selected as hub genes, including MAP3K4. The expression levels of MAP3K4 were positively correlated with NAFLD activity score (r = 0.702, p = 0.002). Furthermore, we found a positive correlation of MAP3K4 expression with serum total cholesterol (r = 0.564, p = 0.023), uric acid levels (r = 0.520, p = 0.039), and body mass index (r = 0.574, p = 0.020). Downregulation of MAP3K4 decreased LDs accumulation in HepG2 cells and reduced the expression of CGI-58 and Plin-2 by imbibition of JNK and group IVA cytosolic phospholipase A2 (cPLA2) activation. Conclusion The study revealed a number of regulatory genes related to hepatic lipid metabolism of NAFLD, and demonstrated that MAP3K4 played a pivotal role in the hepatic lipogenesis of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease

Bin

Chen

et al. 2022

J Transl Med

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“…IGF/insulin signaling plays an essential role in fetal growth, and mice with altered IGF/insulin signaling have been used in thoroughly researched models of FGR [ 59 ]. In TS cells and the placenta, MAP3K4 is essential for the IGF1R/IR and Akt signaling pathways, and MAP3K4 kinase inactivation causes FGR driven by placental insufficiency [ 60 ].…”

Section: The Role Of Map3k4 In Governing Growth and Development Of Bodymentioning

confidence: 99%

MAP3K4 kinase action and dual role in cancer

Huang,

Wang,

Zhang

et al. 2024

Discov Onc

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It is commonly known that the MAPK pathway is involved in translating environmental inputs, regulating downstream reactions, and maintaining the intrinsic dynamic balance. Numerous essential elements and regulatory processes are included in this pathway, which are essential to its functionality. Among these, MAP3K4, a member of the serine/threonine kinases family, plays vital roles throughout the organism's life cycle, including the regulation of apoptosis and autophagy. Moreover, MAP3K4 can interact with key partners like GADD45, which affects organism's growth and development. Notably, MAP3K4 functions as both a tumor promotor and suppressor, being activated by a variety of factors and triggering diverse downstream pathways that differently influence cancer progression. The aim of this study is to provide a brief overview of physiological functions of MAP3K4 and shed light on its contradictory roles in tumorigenesis.

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“…Abnormal expression of miR520a-5p affects placental development and healthy fetal growth by inhibiting the expression of signaling pathway genes. According to the research byPerry et al (2022) [31], a regulatory action site of miR520a-5p exists in the 3'-UTR of MEK1 and MAPK, and miR520a-5p can negatively regulate the proliferative activity of endothelial cells through MAP2K1/MEK1.…”

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confidence: 99%

Mechanism of MEK1-MAPK Pathway-based MiR520a-5p in Fetal Growth Restriction

Jha

2023

Preprint

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this research was developed to investigate the expression level of miR520a-5p in serum of fetal growth restriction (FGR) and the role of its target genes, mitogen-activated protein kinase (MAPK) and mitogen-activated protein kinase 1 (MEK1), in the pathogenesis of FGR. Thirty cases in the FGR group and 30 cases in the normal birth weight group (control group) were selected. MiR520a-5p expression and its target genes MEK1 and MAPK mRNA in the two groups were detected by RT‒PCR. The protein levels of the target genes MEK1 and MAPK of miR520a-5p were determined by Western blotting. The Spearman grade correlation was used to analyze the correlation between the expression levels of miR520a-5p and MEK1 in serum of FGR group and the correlation between MEK1 and MAPK expression. Compared with the control group, the expression of miR520a-5p in the FGR group was significantly increased (P < 0.05). MEK1 and MAPK mRNA levels of miR520a-5p target genes in the FGR group were drastically reduced (P < 0.05), while their protein levels were decreased (P < 0.05). Spearman rank correlation analysis suggested a negative correlation between miR-520a-5p and MEK1 (r = − 0.667; P < 0.05) and a positive correlation between MEK1 and MAPK (r = 0.46; P < 0.05). MEK1 and MAPK mRNA expressions in fetal growth and development were detected, and the decreased expression of MEK1 and MAPK mRNA was correlated with the pathogenesis of FGR. MiR520a-5p may participate in the pathogenesis of FGR through the MIRR520A-5P-MEK1-MAPK signaling pathway.

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MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway

Cited by 4 publications

References 87 publications

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease

MAP3K4 kinase action and dual role in cancer

Mechanism of MEK1-MAPK Pathway-based MiR520a-5p in Fetal Growth Restriction

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