MSK1 and JNKs mediate phosphorylation of STAT3 in UVA-irradiated mouse epidermal JB6 cells
Open accessAbstract
Phosphorylation of Tyr(705) and Ser(727) of signal transducer and activator of transcription 3 (STAT3) are known to be required for maximal activation by diverse stimuli. Tyr(705) phosphorylation is generally accepted to be mediated by the Janus kinase family. But the mechanism for STAT3 (Ser(727)) phosphorylation is not well understood. Here, we provide evidence that UVA-induced phosphorylation of STAT3 at Ser(727) is inhibited by pretreatment of JB6 cells with PD98059 or SB202190. Phosphorylation of STAT3 (Ser(727)) is also markedly prevented by a dominant negative mutant of ERK2, c-Jun N-terminal kinase 1 (JNK1), or p38 kinase and in knockout Jnk1(-/-) or Jnk2(-/-) cells. Furthermore, STAT3 (Ser(727)) phosphorylation is suppressed by C- or N-terminal "kinase-dead" mutants of mitogen- and stress-activated protein kinase 1 (MSK1), a downstream kinase of ERKs and p38 kinase, and H89, a potential MSK1 inhibitor. In vitro experiments showed that active MSK1 and JNKs, but not ERKs or p38 kinase, phosphorylate STAT3 (Ser(727)). Additionally, the role of MAPKs in mediating UVA-stimulated DNA binding activity of STAT3 was investigated. Overall, these results suggest that UVA-induced Ser(727) phosphorylation of STAT3 may occur through MSK1 and JNKs.
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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 Zhang et al., 2001
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Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases
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“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, enha…”
BackgroundInfluential
- Authors
- Zhang, Y., Liu, G., & Dong, Z.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Dong, Zigang
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 45
- Pages
- 42534-42542
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2158222731
- Cited by
- 81
- References
- 4
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Hormel Foundation (CA77646, CA81064, CA74916)
- National Institutes of Health (CA81064)
- National Cancer Institute (R29CA074916, CA 74916, R01CA077646, CA-81064, CA 77646)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT3, MSK1, JNK1, JNK2, UVA irradiation, MAPK signaling, ERK2, p38 MAPK, PD98059, SB202190, H89, transcriptional activation, DNA-binding activity
- MeSH terms
- Animals, Cells, Cultured, DNA-Binding Proteins, Epidermis, Phosphorylation, Serine, Ultraviolet Rays, Trans-Activators, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Ribosomal Protein S6 Kinases, 90-kDa, JNK Mitogen-Activated Protein Kinases, STAT3 Transcription Factor, Mice, ErbB Receptors
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