| Project/Area Number |
13660340
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Nagoya University |
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Principal Investigator |
AOKI Naohito Nagoya University, Graduate School of Bioagricultural Sciences, Assistant Professor, 大学院・生命農学研究科, 助手 (40242846)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | protein tyrosine phophatase / PTP1B / STAT5 / prolactin signaling / TC-PTP |
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| Research Abstract |
It has been shown that a cytoplasmic PTP1B can dephosphorylate STAT5a and STAT5b in cytosol, thereby negatively regulating prolactin receptor-mediated signal transduction pathway. To extend these findings, we next focused on TC-PTP, because it has high structural similarity to PTP1B and comprises a PTP subfamily with PTP1B. TC-PTP could dephosphorylate STAT5a and STAT5b, but the apparent dephosphoryiation activity of TC-PTP was weaker than that of cytosolic PTP1B 30 min after PRL stimulation in transfected COS-7 cells, whereas both STAT5a and STAT5b were dephosphorylated to the same extent by rccombinant TC-PTP and PTP1B in vitro. Tyrosine-phosphorylated STAT5 was coimmunoprecipitated with substrate trapping mutants of TC-PTP, suggesting that STAT5 is a specific substrate of TC-PTP. These observations were further extended in mammary epithelial COMMA-1D cells stably expressing TC-PTP. A time-course study revealed that dephosphorylation of STAT5 by TC-PTP was delayed compared with that by cytosolic PTP1B due to nuclear localization of TC-PTP throughout PRL stimulation in mammary epithelial cells. Endogenous beta-casein gene expression and beta-casein gene promoter activation in COS-7 cells were largely suppressed by TC-PTP wild type as well as catalytically inactive mutants, suggesting that stable complexes formed between STAT5 and TC-PTP in the nucleus. Taken together, we conclude thai TC-PTP is catalytically competent with respect to dephosphorylation and deactivation of PRL-activated STAT5 in the nucleus.
Further studies also revealed that TC-PTP can dephosphorylate IL-3 receptor-activated STAT3 in nucleus. Taken together, TC-PTP plays a critical role in JAK-STAT signaling pathways.
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