Role of endothelin-1, sodium hydrogen exchanger-1 and mitogen activated protein kinase (MAPK) activation in glucose-induced cardiomyocyte hypertrophy

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

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Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity

The Journal of Cell Biology ◽

10.1083/jcb.201305049 ◽

2014 ◽

Vol 204 (6) ◽

pp. 891-900 ◽

Cited By ~ 24

Author(s):

Ibtissem Nabti ◽

Petros Marangos ◽

Jenny Bormann ◽

Nobuaki R. Kudo ◽

John Carroll

Keyword(s):

Protein Kinase ◽

Spindle Assembly Checkpoint ◽

Mitogen Activated Protein Kinase ◽

Cyclin Dependent Kinase ◽

Anaphase Promoting Complex ◽

Female Meiosis ◽

Dual Mode ◽

Mitogen Activated Protein ◽

Meiosis I

Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes.

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Role of p38 mitogen‐activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs

Reviews in Medical Virology ◽

10.1002/rmv.2217 ◽

2021 ◽

Author(s):

Yogesh Chander ◽

Ram Kumar ◽

Nitin Khandelwal ◽

Namita Singh ◽

Brij Nandan Shringi ◽

...

Keyword(s):

Protein Kinase ◽

Virus Replication ◽

Broad Spectrum ◽

Antiviral Drugs ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Protein Kinase Signalling

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Endothelins stimulate mitogen-activated protein kinase cascade through either ETA or ETB

AJP Cell Physiology ◽

10.1152/ajpcell.1994.267.4.c1130 ◽

1994 ◽

Vol 267 (4) ◽

pp. C1130-C1135 ◽

Cited By ~ 45

Author(s):

Y. Wang ◽

P. M. Rose ◽

M. L. Webb ◽

M. J. Dunn

Keyword(s):

Protein Kinase ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Mapk Cascade ◽

Mitogen Activated Protein Kinase ◽

Thymidine Uptake ◽

Mapk Activation ◽

Transfected Cells ◽

Gel Retardation ◽

Mitogen Activated Protein

Endothelin (ET) has been shown to activate mitogen-activated protein kinase (MAPK). However, it has been unclear which of the ET receptors is coupled to MAPK activation. In the present study, we conducted experiments to determine which ET receptor is linked to MAPK activation. We found that both human ETA and ETB were coupled to the MAPK cascade in ETA or ETB cDNA-transfected Chinese hamster ovary cells. ET-1 was more potent than ET-3 in the activation of p42 MAPK, induction of MAPK kinase (MAPKK) gel retardation and uptake of [3H]thymidine in ETA-transfected cells, whereas sarafotoxin (S6c) showed no stimulatory effect on the kinases and [3H]thymidine uptake. ET-1, ET-3, and S6c had approximately the same potency to activate p42 MAPK, MAPKK gel retardation, and [3H]thymidine uptake in ETB-transfected cells. These data suggest that 1) ET isopeptides, through either ETA or ETB receptors, induce the MAPK cascade as well as cell proliferation; and 2) the different potencies of ET isopeptides for activation of the MAPK cascade and induction of cell growth are mainly due to their different affinities toward ETA and ETB.

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