2003 Fiscal Year Final Research Report Summary
Roles of serine phosphorylation of thrombopoietin receptor
| Project/Area Number |
13671085
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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 |
Hematology
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| Research Institution | Keio University |
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Principal Investigator |
MIYAKAWA Yoshitaka Keio University, School of Medicine, Assistant professor, 医学部, 専任講師 (50250238)
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| Co-Investigator(Kenkyū-buntansha) |
KIZAKI Masahiro Keio University, School of Medicine, Associate professor, 医学部, 専任講師 (20161432)
IKEA Yasuo Keio University, School of Medicine, 医学部, 教授 (00110883)
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| Project Period (FY) |
2001 – 2003
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| Keywords | thrombopoietin / megakaryocyte / Phosphorylation / hematopoiesis |
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| Research Abstract |
c-Mpl is a cognate receptor for a cytokine, thrombopoietin, which regulates Megakaryopoiesis and thrombopoieis in vivo. Thrombopoietin induces the activation of Jak2, Tyk2, PI3 kinase, MAP kinase in Mpl-expressing cell lines and normal megakaryocytes. When the serine residues of Mpl were altered with alanine, the proliferation of BaF3 cells expressing those mutants were suppressed compared to the wild type Mpl. The serine residues were constitutively phosphorylated and its phosphorylation was enhanced after stimulation with thrombopoietin. We also confirmed the expression of GFP protein in primary megakaryocytes using retrovirus, and this system should be useful to analyze the function of Mpl mutants in primary cells. The promoter region of thrombopoietin was analyzed by reporter assays. We found retinoic acid regulates the transcription of thrombopoietin gene.
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