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Cited by 1,974Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation

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Wen, Zilong, Zhong, Zhong, Darnell, James E·1995·Cell
DOI 10.1016/0092-8674(95)90311-9
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Abstract

Stat1 and Stat3 are latent transcriptional factors activated initially through phosphorylation on single tyrosine residues induced by cytokine and growth factor occupation of cell surface receptors. Here we show that phosphorylation on a single serine (residue 727) in each protein is also required for maximal transcriptional activity. Both cytokines and growth factors are capable of inducing the serine phosphorylation of Stat1 and Stat3. These experiments show that gene activation by Stat1 and Stat3, which obligatorily require tyrosine phosphorylation to become active, also depends for maximal activation on one or more of the many serine kinases.

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Crossref · 10.1016/0092-8674(95)90311-9

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  • IL-6 signalling through gp130 activates JAK and STAT, leading to expression of target genes such as SOCS3.

    “In both pathways, the activated IL‐6R‐gp130 complex binds and activates the Janus kinase (JAK) family of tyrosine kinases, primarily JAK1, JAK2, and TYK2, which phosphorylate the cytoplasmatic tail of gp130, enabling the association of the Signal Transducer and Activator of Transcription (STAT), mainly STAT1 and STAT3.”

    From Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting (2022) · cites this paper as [17]

  • Generally, S727 phosphorylation is suggested to work with Y705 phosphorylation to activate STAT3-mediated transcription, most likely through recruiting coactivator proteins.

    “Generally, pS is suggested to work with pY to activate STAT3-mediated transcription (Wen et al., 1995; Abe et al., 2001; Shen et al., 2004) most likely through recruiting coactivator proteins (Schuringa et al., 2001; Lufei et al., 2007; Lee et al., 2009a), e.g., JNK1/2-mediated pS-STAT3 following UVA irradiation, enhanced STAT3–DNA binding in epidermal JB6 cells (Zhang et al., 2001; Liu et al., 2”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Wen et al., 1995

  • S727 phosphorylation of STAT3 is mediated by various serine/threonine kinases depending on the stimulus, upstream signaling pathway, and cell type.

    “In addition to phosphorylation on Y705, STAT3 can be phosphorylated on Ser727 within its TAD (Wen et al., 1995) by various serine/threonine kinases, e.g., mitogen-activated protein kinase (MAPK) like MAPK kinase/ERK (Chung et al., 1997; Stephens et al., 1998; Ng et al., 2011), c-Jun N-terminal kinase (JNK) (Zhang et al., 2001; Liu et al., 2012), p38 (Gollob et al., 1999; Lim and Cao, 1999; Turkson”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Wen et al., 1995

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Authors
Wen, Z., Zhong, Z., & Darnell, J. E.
Affiliations
Rockefeller University (US)
ORCID
Wen, Zilong
Venue
Cell
Publisher
Elsevier BV
Published
1995-07
Volume
82
Issue
2
Pages
241-250
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/0092-8674(95)90311-9
OpenAlex
W2030865745
Cited by
1,974
References
2
Citations by year
2026: 21 · 2025: 27 · 2024: 41 · 2023: 38 · 2022: 36 · 2021: 48 · 2020: 46 · 2019: 58 · 2018: 59 · 2017: 50 · 2016: 55 · 2015: 53 · 2014: 69 · 2013: 81 · 2012: 68
FWCI
43.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • Cancer Research Institute
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI032489, AI32489)
  • University of Colorado School of Medicine, Anschutz Medical Campus
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
STAT1, STAT3, serine phosphorylation, tyrosine phosphorylation, transcriptional activation, cytokine signaling, growth factor signaling, serine kinase, transcription factors
MeSH terms
Amino Acid Sequence, Animals, Cell Line, Chlorocebus aethiops, DNA-Binding Proteins, Gene Expression Regulation, Humans, Luciferases, Molecular Sequence Data, Phosphorylation, Phosphoserine, Recombinant Proteins, Serine, Transcription Factors, Transcription, Genetic, Transfection, Tyrosine, Signal Transduction, Transcriptional Activation, Trans-Activators, 3T3 Cells, Conserved Sequence, Sequence Homology, Amino Acid, Phosphotyrosine, STAT1 Transcription Factor, STAT3 Transcription Factor, Mice

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