Stat3: a STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6

Zhong, Zhong; Wen, Zilong; Darnell, James E.

doi:10.1126/science.8140422

Cited by 2,070Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

Stat3: a STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6

Zhong, Zhong, Wen, Zilong, Darnell, James E.·1994·Science

DOI 10.1126/science.8140422

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Abstract

The STAT family of proteins carries out a dual function: signal transduction and activation of transcription. A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor (EGF) and interleukin-6 (IL-6) but not interferon gamma (IFN-gamma). It is likely that this phosphoprotein forms homodimers as well as heterodimers with the first described member of the STAT family, Stat91 (renamed Stat1 alpha), which is activated by the IFNs and EGF. Differential activation of different STAT proteins in response to different ligands should help to explain specificity in nuclear signaling from the cell surface.

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FGF19 administration failed to induce hepatic expression of EGF, IL-10, IL-21, IL-22 and IL-31.
“In addition, FGF19 administration failed to induce hepatic expression of a panel of growth factors and cytokines associated with increased pSTAT3 signalling, including epidermal growth factor (EGF)31, IL-10 (ref. 32), IL-21 (ref. 33), IL-22 (ref. 34) and IL-31 (ref. 35)”
From Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis (2017) · cites this paper as [31]
Phosphorylation of STAT3 on tyrosine 705 (Y705) by various upstream kinases is critical for STAT3 activation.
“Phosphorylation of STAT3 on tyrosine 705 (Y705) by various upstream kinases is critical for STAT3 activation.3”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [3]

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Authors: Zhong, Z., Wen, Z., & Darnell, J. E.
Affiliations: Rockefeller University (US)
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021.
ORCID: Wen, Zilong
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1994-04
Volume: 264
Issue: 5155
Pages: 95-98
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.8140422
OpenAlex: W1981799488
Cited by: 2,070
References: 1
Citations by year: 2026: 21 · 2025: 47 · 2024: 42 · 2023: 70 · 2022: 59 · 2021: 75 · 2020: 73 · 2019: 69 · 2018: 55 · 2017: 82 · 2016: 71 · 2015: 75 · 2014: 90 · 2013: 92 · 2012: 70
FWCI: 45.03
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01AI032489, AI32489)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: STAT3, STAT family, tyrosine phosphorylation, epidermal growth factor, interleukin-6, interferon-gamma, signal transduction, transcriptional activation, DNA binding, homodimerization, heterodimerization, ligand specificity
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Line, DNA, DNA-Binding Proteins, Epidermal Growth Factor, Humans, Interferon-gamma, Molecular Sequence Data, Phosphorylation, Regulatory Sequences, Nucleic Acid, Transfection, Tumor Cells, Cultured, Tyrosine, Trans-Activators, Interleukin-6, Sequence Alignment, STAT1 Transcription Factor, STAT3 Transcription Factor, Mice

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Stat3: a STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6

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