ArticleThe Biochemical journal2000
Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rac-1 and the kinase SEK-1/MKK-4 as signal transduction components.
Article in The Biochemical journal, 2000. 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.
- Article
- Out of Nucleus: Serine 727 Phosphorylation Orchestrates Non-Canonical STAT3 Functions-Relevance to Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Review
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- CENPs in hepatocellular carcinoma: a comprehensive review of expression patterns, clinical correlations, and functional mechanisms.American journal of cancer research · 2025Review
- STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness.Scientific reports · 2023Article
- Prognostic comparative genes predict targets for sorafenib combination therapies in hepatocellular carcinoma.Computational and structural biotechnology journal · 2022Article
- Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia.Scientific reports · 2021Article
- The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients' Survival Time.Frontiers in cell and developmental biology · 2021Article
- Granulocyte-macrophage colony-stimulating factor negatively regulates early IL-10-mediated responses.Future science OA · 2018Article
- Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration.Scientific reports · 2017Article
- OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3 signaling.Oncotarget · 2017Article
- LIF signal in mouse embryonic stem cells.JAK-STAT · 2015Review
- A complex signaling network involving protein kinase CK2 is required for hepatitis C virus core protein-mediated modulation of the iron-regulatory hepcidin gene expression.Cellular and molecular life sciences : CMLS · 2014Article
- Article
- Interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by JAK2- and PI3K-induced STAT1/3 in HepG2 hepatocyte cells.Molecular and cellular biochemistry · 2014Article
- PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.Theranostics · 2014Review
- LIF-STAT signaling and trophoblast biology.JAK-STAT · 2013Review
- Intranuclear crosstalk between extracellular regulated kinase1/2 and signal transducer and activator of transcription 3 regulates JEG-3 choriocarcinoma cell invasion and proliferation.TheScientificWorldJournal · 2013Article
- STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway.Journal of biosciences · 2012Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study, signal transducer and activator of transcription 3 (STAT3) Ser(727) phosphorylation and transactivation was investigated in relation to activation of mitogen-activated protein (MAP) kinase family members including extracellular-signal-regulated protein kinase (ERK)-1, c-Jun N-terminal kinase (JNK)-1 and p38 ('reactivating kinase') in response to interleukin (IL)-6 stimulation. Although IL-6 can activate ERK-1 in HepG2 cells, STAT3 transactivation and Ser(727) phosphorylation were not reduced by using the MAP kinase/ERK kinase (MEK) inhibitor PD98059 or by overexpression of dominant-negative Raf. IL-6 did not activate JNK-1 in HepG2 cells and STAT3 was a poor substrate for JNK-1 activated by anisomycin, excluding a role for JNK1 in IL-6-induced STAT3 activation. However, SEK-1/MKK-4 [where SEK-1 stands for stress-activated protein kinase (SAPK)/ERK kinase 1, and MKK-4 stands for MAP kinase kinase 4] was activated in response to IL-6 and overexpression of dominant-negative SEK-1/MKK-4(A-L) reduced both IL-6-induced STAT3 Ser(727) phosphorylation as well as STAT3 transactivation. Subsequently, the SEK-1/MKK-4 upstream components Vav, Rac-1 and MEKK were identified as components of a signal transduction cascade that leads to STAT3 transactivation in response to IL-6 stimulation. Furthermore, inhibition of p38 kinase activity with the inhibitor SB203580 did not block STAT3 Ser(727) phosphorylation but rather increased both basal as well as IL-6-induced STAT3 transactivation, indicating that p38 may act as a negative regulator of IL-6-induced STAT3 transactivation through a presently unknown mechanism. In conclusion, these data indicate that IL-6-induced STAT3 transactivation and Ser(727) phosphorylation is independent of ERK-1 or JNK-1 activity, but involves a gp130 receptor-signalling cascade that includes Vav, Rac-1, MEKK and SEK-1/MKK-4 as signal transduction components.
Indexed as
Identifiers
10727406PMC1220935What OpenQuestion holds
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.