The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
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Yamamoto T, Sekine Y, Kashima K, Kubota A, Sato N, Aoki N, Matsuda T
The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
Biochem Biophys Res Commun. 2002 Oct 4;297(4):811-7.
- PubMed ID
- 12359225 [ View in PubMed]
- 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.