Two Signals Are Necessary for Cell Proliferation Induced by a Cytokine Receptor gp130: Involvement of STAT3 in Anti-Apoptosis
Open accessAbstract
gp130 is a common signal transducer for the interleukin-6-related cytokines. To delineate the gp130-mediated growth signal, we established a series of pro-B cell lines expressing chimeric receptors composed of the extracellular domain of the granulocyte colony-stimulating factor receptor and the transmembrane and cytoplasmic domains of gp130. The second tyrosine (from the membrane) of gp130, which was required for the tyrosine phosphorylation of SHP-2, its association with GRB2, and activation of a MAP kinase, was essential for mitogenesis, but not for anti-apoptosis. On the other hand, the tyrosine in the YXXQ motifs essential for STAT3 activation was required for bcl-2 induction and anti-apoptosis. Furthermore, dominant-negative STAT3 inhibited anti-apoptosis. These data demonstrate that two distinct signals, mitogenesis and anti-apoptosis, are required for gp130-induced cell growth and that STAT3 is involved in anti-apoptosis.
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Phosphorylation of gp130 leads to dimerization of gp130 and activation of STAT1 and STAT3 as well as the SHP2-RAS-MAPK pathway.
“The phosphorylation of gp130 leads to dimerization of gp130 and activation of STAT1 and STAT3 as well as the SHP2-RAS-MAPK pathway (where SHP2 is Src homology 2 [SH2] domain-containing protein tyrosine phosphatase) (20-22).”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [22]
STAT3 transcriptionally activates genes of several anti-autophagy-related proteins e.g., BCL2, BCL2L1, and MCL1.
“STAT3 transcriptionally activates genes of several anti-autophagy–related proteins e.g., BCL2, BCL2L1, and MCL1 (Fukada et al., 1996; Bromberg et al., 1999; Bowman et al., 2000).”
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 Fukada et al., 1996
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- Authors
- Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K., & Hirano, T.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Hirano, Toshio
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1996-11
- Volume
- 5
- Issue
- 5
- Pages
- 449-460
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1988917700
- Cited by
- 652
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 10 · 2017: 24 · 2016: 11 · 2015: 15 · 2014: 16 · 2013: 15 · 2012: 22
- FWCI
- 16.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- gp130, STAT3, interleukin-6 family cytokines, chimeric receptors, granulocyte colony-stimulating factor receptor, SHP2, Grb2, mitogen-activated protein kinase, tyrosine phosphorylation, Bcl-2, apoptosis inhibition, mitogenesis, cell proliferation, dominant-negative STAT3
- MeSH terms
- Animals, Cell Division, Cell Line, DNA-Binding Proteins, Humans, Membrane Glycoproteins, Recombinant Fusion Proteins, Signal Transduction, Trans-Activators, Antigens, CD, Proto-Oncogene Proteins c-myc, Apoptosis, STAT3 Transcription Factor, Cytokine Receptor gp130, Mice
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