ArticleMolecular endocrinology (Baltimore, Md.)2015
Serine-727 phosphorylation activates hypothalamic STAT-3 independently from tyrosine-705 phosphorylation.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Hypomethylation of GNA15 Promotes Pancreatic Ductal Adenocarcinoma Progression and Macrophage M2 Polarization via STAT3-CXCL8 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms of Action of Propofol in Modulating Microglial Activation in Ischemic Stroke.Molecules (Basel, Switzerland) · 2025Review
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- STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer.Journal of hematology & oncology · 2021Review
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells.Journal of Cancer · 2020Article
- Insulin-like growth factor-1 acts as a zeitgeber on hypothalamic circadian clock gene expression via glycogen synthase kinase-3β signaling.The Journal of biological chemistry · 2018Article
- Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1.International journal of molecular sciences · 2018Article
- Article
- Exchange factors directly activated by cAMP mediate melanocortin 4 receptor-induced gene expression.Scientific reports · 2016Article
- Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcriptional activity of signal transducer and activator of transcription-3 (STAT-3) is a key element in the central regulation of appetite and energy homeostasis. Activation of hypothalamic STAT-3 has been attributed to cytokine-promoted phosphorylation at tyrosine-705 (Tyr-705). In nonhypothalamic cells, STAT-3 is also phosphorylated at serine-727 (Ser-727), but the functional significance of Ser-727 in the regulation of hypothalamic STAT-3 is not known. We used 2 hypothalamic cell lines and analyzed the effects of various hormones on STAT-3-dependent reporter gene activity and observed that IFN-γ, epidermal growth factor (EGF), and bradykinin (BK) induce similar STAT-3 reporter activation. EGF and BK solely increased Ser-727 and IFN-γ increased Tyr-705 phosphorylation of STAT-3. Specific inhibition of ERK-1/2 activity blocked EGF- and BK-induced STAT-3 activation and Ser-727 phosphorylation. BK-induced ERK-1/2 activation occurred via EGF receptor transactivation. Consequently, the BK-mediated effects on STAT-3 were blocked by a specific EGF receptor antagonist. Next, we analyzed the effects of IFN-γ and EGF on the expression of the STAT-3-dependent genes thyroliberin-releasing hormone and suppressors of cytokine signaling-3. EGF but not IFN-γ enhanced thyroliberin-releasing hormone expression via STAT-3. With regard to suppressors of cytokine signaling-3, we observed prolonged expression induced by IFN-γ and a transient effect of EGF that required coactivation of the activator protein-1. Thus, EGF-promoted Ser-727 phosphorylation by ERK-1/2 is not only sufficient to fully activate hypothalamic STAT-3, but, in terms of targeted genes and required cofactors, entails distinct modes of STAT-3 actions compared with IFN-γ-induced Tyr-705 phosphorylation.
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