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The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
Title: | The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. |
Authors: | Yamamoto, Tetsuya Browse this author | Sekine, Yuichi Browse this author | Kashima, Keiichi Browse this author | Kubota, Atsuko Browse this author | Sato, Noriko Browse this author | Aoki, Naohito Browse this author | Matsuda, Tadashi Browse this author |
Keywords: | IL-6 | T-cell protein-tyrosine phosphatase (TC-PTP) | Signal transducer and activator of transcription (STAT3) | Leukemia inhibitory factor (LIF) |
Issue Date: | 4-Oct-2002 |
Publisher: | Elsevier |
Journal Title: | Biochemical and Biophysical Research Communications |
Volume: | 297 |
Issue: | 4 |
Start Page: | 811 |
End Page: | 817 |
Publisher DOI: | 10.1016/S0006-291X(02)02291-X |
PMID: | 12359225 |
Abstract: | 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. |
Relation: | http://www.sciencedirect.com/science/journal/0006291X |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/28124 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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