The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation
Open accessAbstract
In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. In this study, we examined the involvement of the nuclear isoform of TC-PTP in interleukin-6 (IL-6)-mediated signaling pathway. IL-6 is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions, and has also implicated in IL-6-related diseases. Here, we demonstrate that IL-6-induced tyrosine-phosphorylation and activation of STAT3 were suppressed by overexpression of the nuclear isoform of TC-PTP in 293T cells. Tyrosine-phosphorylated STAT3 directly interacted with a substrate-trapping mutant of TC-PTP. Furthermore, retrovirus-mediated overexpression of the nuclear isoform of TC-PTP suppressed the IL-6-induced growth arrest of myeloid leukemia M1 cells. Endogenous TC-PTP complexed with STAT3 in the nucleus of M1 cells. These results strongly suggest that the nuclear isoform of TC-PTP may serve as a negative regulator of IL-6-mediated signaling pathway.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Deactivation of nuclear STAT3 is mediated by phosphatases.
“Deactivation of nuclear STAT3 was suggested to be mediated by phosphatases (Yamamoto et al., 2002).”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Yamamoto et al., 2002
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Specific Inhibition of Stat3 Signal Transduction by PIAS3
Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P., & Shuai, K. (1997) · Science · doi:10.1126/science.278.5344.1803 · Cited by 980 · see citing works
You, M., Yu, D.-H., & Feng, G.-S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.2416 · Cited by 364 · see citing works
SCHAPER, F., GENDO, C., ECK, M., SCHMITZ, J., GRIMM, C., ANHUF, D., KERR, I. M., & HEINRICH, P. C. (1998) · Biochemical Journal · doi:10.1042/bj3350557 · Cited by 178 · cited 1× · see citing works
“Src homology 2-containing phosphatase 2 (SHP-2) involved in the down regulation of Jak-STAT signaling activated by several cytokines (29, 30, 31).”
BackgroundKim, H., Hawley, T. S., Hawley, R. G., & Baumann, H. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.3.1525 · Cited by 119 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- T. Matsuda, T. Hirano, Interleukin 6 in Cytokine Reference (Oppenheim, J., J., and Feldmann, M., eds), (2000) pp537-563, Academic Press, London
- D. E. Cool, N. K. Tonks, H. Charbonneau, K. A. Walsh, E. . Fischer, E. G. Krebs, cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family, Proc. Natl. Acad. Sci. USA 86 (1989) 5257-5261.
- D. E. Cool, , N. K. Tonks, H. Charbonneau, E. H. Fischer, E. G. Krebs, Expression of a human T-cell protein-tyrosine-phosphatase in baby hamster kidney cells, Proc. Natl. Acad. Sci. USA 87 (1990) 7280-7284.
- B. Mosinger. Jr., U. Tillmann, H. Westphal, M. L. Tremblay, Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase, Proc. Natl. Acad. Sci. USA 89 (1992) 499-503.
Cited by
Sorted by citations
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272 · see citing works
Bonetto, A., Aydogdu, T., Jin, X., Zhang, Z., Zhan, R., Puzis, L., Koniaris, L. G., & Zimmers, T. A. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00039.2012 · Cited by 463 · see citing works
Ng, I. H. W., Ng, D. C. H., Jans, D. A., & Bogoyevitch, M. A. (2012) · Biochemical Journal · doi:10.1042/bj20120941 · Cited by 63 · see citing works
“Supporting this, a combination of results from binding assays using a catalytically inactiveTC45mutantanddeletionstudiesofSTAT3 α indicatedan interaction between the C-terminal domain of STAT3 α and TC45 [34].”
BackgroundSobotta, S., Raue, A., Huang, X., Vanlier, J., Jünger, A., Bohl, S., Albrecht, U., Hahnel, M. J., Wolf, S., Mueller, N. S., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00775 · Cited by 28 · see citing works
“Deactivation of nuclear STAT3 was suggested to be mediated by phosphatases (Yamamoto et al., 2002).”
BackgroundCritical analysis of the potential for targeting STAT3 in human malignancy
Grandis, J., & Peyser (2013) · OncoTargets and Therapy · doi:10.2147/ott.s47903 · Cited by 24 · see citing works
“Other proteins, including GRIM-19, can also abrogate STAT3 activity via direct interactions.”
- Authors
- Yamamoto, T., Sekine, Y., Kashima, K., Kubota, A., Sato, N., Aoki, N., & Matsuda, T.
- Affiliations
- Hokkaido University (JP)
- Nagoya University (JP)
- Corresponding author
- Matsuda, Tadashi
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 297
- Issue
- 4
- Pages
- 811-817
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2167070735
- Cited by
- 250
- References
- 4
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 13 · 2015: 9 · 2014: 11 · 2013: 15 · 2012: 29
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- TCPTP, IL-6 signaling, STAT3 dephosphorylation, STAT3 tyrosine phosphorylation, negative regulation of cytokine signaling
- MeSH terms
- Acute-Phase Proteins, Animals, Cell Division, Cell Line, Cell Nucleus, DNA-Binding Proteins, Humans, Isoenzymes, Kinetics, Luciferases, Phosphorylation, Recombinant Proteins, Substrate Specificity, Transfection, Tumor Cells, Cultured, Signal Transduction, Trans-Activators, Interleukin-6, Polymerase Chain Reaction, Protein Tyrosine Phosphatases, Genes, Reporter, STAT3 Transcription Factor, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
