ArticleRespiratory research2016
Protein tyrosine phosphatase PTP-RR regulates corticosteroid sensitivity.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?Frontiers in cell and developmental biology · 2022Review
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- [Liver failure and glucocorticoid resistance].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma.Biomolecules · 2020Article
- [Pathogenesis of steroid-resistant asthma and the influence of vitamin D].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Review
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundWe have recently reported that protein phosphate 2A (PP2A) inactivation resulted in increased phosphorylation of the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase 1 (JNK1) and glucocorticoid receptors (GR) at Ser(226), thereby reducing GR nuclear translocation and causing corticosteroid insensitivity in severe asthmatics. Protein tyrosine phosphatases (PTPs) are also known to be critically involved in the regulation of MAPKs, such as JNK and therefore potentially associated with GR function. The aim of study was to elucidate the involvement of MAPK-PTPs (PTP-RR, PTP-N5 and PTP-N7), which can dephosphorylate MAPKs, in the regulation of corticosteroid sensitivity.
methodsCorticosteroid sensitivity, GR nuclear translocation, phosphorylation levels of GR-Ser(226), JNK1 and PP2A catalytic subunit (PP2AC)-Tyr(307) and protein expression levels and activities of PTP-RR and PP2AC were evaluated in U937 cells and/or peripheral blood mononuclear cells (PBMCs). Knock-down effects of MAPK-PTPs using siRNA were also evaluated.
resultsKnock-down of PTP-RR, but not of PTP-N5 or PTP-N7 impaired corticosteroid sensitivity, induced GR-Ser(226) phosphorylation and reduced GR nuclear translocation. Under IL-2/IL-4-induced corticosteroid insensitivity, PTP-RR expression, activity and associations with JNK1 and GR were reduced but PTP-RR activity was restored by formoterol. Also in PBMCs from severe asthmatic patients, PTP-RR and JNK1 expression were reduced and GR-Ser(226) phosphorylation increased. Furthermore, PTP-RR was associated with PP2A. PTP-RR reduction enhanced PP2AC-Tyr(307) phosphorylation leading to impairment of PP2A expression and activity.
conclusionsWe demonstrated that with corticosteroid insensitivity PTP-RR fails to reduce phosphorylation of JNK1 and GR-Ser(226), resulting in down-regulation of GR nuclear translocation. Reduced PTP-RR may represent a novel cause of corticosteroid insensitivity in severe asthmatics.
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