ArticleThe Journal of biological chemistry2013
Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Pdcd4-Rictor interaction suppresses mTORC2-PFKFB3 axis and tumorigenesis in NSCLC.Neoplasia (New York, N.Y.) · 2026Article
- Pdcd4-Rictor Interaction Suppresses PFKFB3 to inhibit Tumorigenesis.Research square · 2026Article
- Article
- Bioinformatic meta-analysis reveals novel differentially expressed genes and pathways in sarcoidosis.Frontiers in medicine · 2024Article
- AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo.Journal of biological engineering · 2021Article
- Effects of Rapamycin on Insulin Brain Endothelial Cell Binding and Blood-Brain Barrier Transport.Medical sciences (Basel, Switzerland) · 2021Article
- Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1.International journal of molecular medicine · 2021Article
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- MKP-1 Modulates Mitochondrial Transcription Factors, Oxidative Phosphorylation, and Glycolysis.ImmunoHorizons · 2020Article
- MAP kinase phosphatase-1, a gatekeeper of the acute innate immune response.Life sciences · 2020Review
- The KRASCancer discovery · 2020Article
- Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance.American journal of physiology. Cell physiology · 2019Review
- Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity.Archives of toxicology · 2019Article
- MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Rapamycin in ischemic stroke: Old drug, new tricks?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Review
- Paradoxical LTP maintenance with inhibition of protein synthesis and the proteasome suggests a novel protein synthesis requirement for early LTP reversal.Journal of theoretical biology · 2018Article
- K63-Linked Polyubiquitination on TRAF6 Regulates LPS-Mediated MAPK Activation, Cytokine Production, and Bacterial Clearance in Toll-Like Receptor 7/8 Primed Murine Macrophages.Frontiers in immunology · 2018Article
- The dataset describes: HIF-1 α expression and LPS mediated cytokine production in MKP-1 deficient bone marrow derived murine macrophages.Data in brief · 2017Article
- Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype.Free radical biology & medicine · 2017Review
- MKP-1 negatively regulates LPS-mediated IL-1β production through p38 activation and HIF-1α expression.Cellular signalling · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Mitogen-activated protein kinase phosphatase-1 (MKP-1), also known as dual specificity phosphatase-1 (DUSP-1), plays a crucial role in the deactivation of MAPKs. Several drugs with immune-suppressive properties modulate MKP-1 expression as part of their mechanism of action. We investigated the effect of mTOR inhibition through rapamycin and a dual mTOR inhibitor (AZD2014) on MKP-1 expression. Low dose rapamycin led to a rapid activation of both AKT and ERK pathways with a subsequent increase in MKP-1 expression. Rapamycin treatment led to phosphorylation of CREB, transcription factor 1 (ATF1), and ATF2, three transcription factors that bind to the cyclic AMP-responsive elements on the Mkp-1 promoter. Inhibition of either the MEK/ERK or the AKT pathway attenuated rapamycin-mediated MKP-1 induction. AZD2014 did not activate AKT but activated the ERK pathway, leading to a moderate MKP-1 induction. Using bone marrow-derived macrophages (BMDMs) derived from wild-type (WT) mice or mice deficient in AKT1 and AKT2 isoforms or BMDM from targeted deficiency in MEK1 and MEK2, we show that rapamycin treatment led to an increased MKP1 expression in BMDM from WT but failed to do so in BMDMs lacking the AKT1 isoform or MEK1 and MEK2. Importantly, rapamycin pretreatment inhibited LPS-mediated p38 activation and decreased nitric oxide and IL-6 production. Our work provides a conceptual framework for the observed immune modulatory effect of mTOR inhibition.
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