ArticleThe Journal of biological chemistry2009
Glucocorticoid-mediated inhibition of Lck modulates the pattern of T cell receptor-induced calcium signals by down-regulating inositol 1,4,5-trisphosphate receptors.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- Article
- Dexamethasone improves thymoma-associated myasthenia gravis via the AKT-mTOR pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- CaBiomolecules · 2023Review
- The Complex Effects of PKM2 and PKM2:IPCells · 2023Article
- A Novel Peptide that Disrupts the Lck-IPArchives of microbiology & immunology · 2023Article
- Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia.Science advances · 2022Article
- Type of PaperY192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection.International journal of molecular sciences · 2022Article
- Bcl-xL acts as an inhibitor of IPCell death and differentiation · 2022Article
- High-dose dexamethasone injection disordered metabolism and multiple protein kinases expression in the mouse kidney.Bioscience reports · 2021Article
- Epidemiologic and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China: A descriptive survey report.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2020Article
- Review
- Autoimmune Diseases in Patients with Cushing's Syndrome after Resolution of Hypercortisolism: Case Reports and Literature Review.International journal of endocrinology · 2018Article
- Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.Pharmacology & therapeutics · 2016Review
- Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies.Oncoimmunology · 2016Article
- Glucocorticoids downregulate Fyn and inhibit IP(3)-mediated calcium signaling to promote autophagy in T lymphocytes.Autophagy · 2010Article
- Apoptosis and autophagy: decoding calcium signals that mediate life or death.Cold Spring Harbor perspectives in biology · 2010Review
- Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia.Cell death and differentiation · 2010Article
- Glucocorticoid receptor: implications for rheumatic diseases.Clinical and experimental rheumatologyReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucocorticoids are potent immunosuppressive agents that block upstream signaling events required for T cell receptor (TCR) activation. However, the mechanism by which glucocorticoids inhibit downstream responses, such as inositol 1,4,5-trisphosphate (IP(3))-induced calcium signals, is not completely understood. Here we demonstrate that low concentrations of dexamethasone rapidly convert transient calcium elevations to oscillations after strong TCR stimulation. Dexamethasone converted the pattern of calcium signaling by inhibiting the Src family kinase Lck, which was shown to interact with and positively regulate Type I IP(3) receptor. In addition, low concentrations of dexamethasone were sufficient to inhibit calcium oscillations and interleukin-2 mRNA after weak TCR stimulation. Together, these findings indicate that by inhibiting Lck and subsequently down-regulating IP(3) receptors, glucocorticoids suppress immune responses by weakening the strength of the TCR signal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.