A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction
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- Yoshifumi Kashii
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Mie Uchida
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Keita Kirito
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Masaru Tanaka
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Kousuke Nishijima
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Masaki Toshima
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Tomoko Ando
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Kazuki Koizumi
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Tomoyuki Endoh
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Ken-ichi Sawada
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Mariko Momoi
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Yasusada Miura
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Keiya Ozawa
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
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- Norio Komatsu
- From the Departments of Pediatrics and Hematology, Jichi Medical School, Tochigi, Japan; Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract
<jats:title>Abstract</jats:title><jats:p>The phosphatidylinositol 3-kinase (PI3K) signaling pathway is important for the regulation of a number of cellular responses. Serine/threonine kinase Akt (protein kinase B; PKB) is downstream of PI3K and activated by growth factors. This study found that erythropoietin (EPO) induced tyrosine phosphorylation of Akt in a time- and dose-dependent manner in EPO-dependent human leukemia cell line UT-7/EPO. In vitro kinase assay using histone H2B and glucose synthase kinase as substrates demonstrated that Akt was actually activated by EPO. EPO-induced phosphorylation of Akt was completely blocked by a PI3K-specific inhibitor, LY294002, at 10 μmol/L, indicating that activation of Akt by EPO is dependent on PI3K activity. In addition, overexpression of the constitutively active form of Akt on UT-7/EPO cells partially blocked apoptosis induced by withdrawal of EPO from the culture medium. This finding suggested that the PI3K-Akt activation pathway plays some role in the antiapoptotic effect of EPO. EPO induced phosphorylation of a member of the trancription factor Forkhead family, FKHRL1, at threonine 32 and serine 253 in a dose- and time-dependent manner in UT-7/EPO cells. Moreover, results showed that Akt kinase activated by EPO directly phosphorylated FKHRL1 protein and that FKHRL1 phosphorylation was completely dependent on PI3K activity as is the case for Akt. In conjunction with the evidence that FKHRL1 is expressed in normal human erythroid progenitor cells and erythroblasts, the results suggest that FKHRL1 plays an important role in erythropoiesis as one of the downstream target molecules of PI3K-Akt.</jats:p>
Journal
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- Blood
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Blood 96 (3), 941-949, 2000-08-01
American Society of Hematology
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Keywords
Details 詳細情報について
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- CRID
- 1361137044612290304
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- ISSN
- 15280020
- 00064971
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- Data Source
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- Crossref