1998 Fiscal Year Final Research Report Summary
Elucidation of signal transduction induced by thrombopoietin.
| Project/Area Number |
09671133
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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 |
ODA Atsushi Keio University School of Medicine, Instructor, 医学部, 助手 (50255436)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Yasuo Keio University School of Medicine, Professor, 医学部, 教授 (00110883)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Thrombopoietin / Crkl / STAT5 / Vav / Erythroipoietin |
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| Research Abstract |
I.We recently reported that thrombopoietin induces tyrosine phosphorylation of Crkl in normal platelets. In this study, we demonstrate that thrombopoietin induces association of Crkl with a tyrosine phosphorylated 95- to lOO-kD protein in platelets and in UT7/TPO cells, a thrombopoietin-dependent megakaryocytic cell line. With specific antibodies against STAT5, we demonstrate that the 95- to lOO-kD protein in Crkl immunoprecipitates is STAT5. Using a beta-casein promoter STATS binding site as a probe, we have also demonstrated that Crkl antisera supershift the STATS-DNA complex, suggesting that Crkl is a component of the complex in the nucleus.Furthermore, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin also induce Crkl-STATS complex formation in responding cells in a stimulation-dependent manner. In vitro, glutathione 5-transferase (GST)-Crkl bound to STATS inducibly through its 5H2 domain.
2. We have reported that collagen and thrombopoietin induce tyrosine phosphorylation of Wiskott-Aldrich syndrome protein in human platelets.
3. We examined signaling by erythropoietin in highly purified human colony forming unit-erythroid cells, generated in vitro from CD34(+) cells.
4. We have reported the generation of truncated forms of TPO by thrombin may be a notable event in view of the platelet-related metabolism of TPO.
5. We have shown that thrombopoietin and other agonists may induce tyrosine phosphorylation of Vav by different mechanisms and Vav may also be involved in signaling during platelet aggregation by its redistribution to the cytoskeleton.
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[Publications] Kato T,Oda A,Inagaki Y,Ohashi H,Matsumoto A,Ozaki K,Miyakawa Y,Watarai H,Fuju K,Kokubo A,Kadoya T,Ikeda Y,Miyazaki H: "Thrombin cleaves recombinant human thrombopoietin : one of the proteolytic events that generates truncated forms of thrombopoietin." Proc Natl Acad Sci USA. 94(9). 4669-4674 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Oda A,Sawada K,Druker BJ,Ozaki K,Takano H,Koizumi K,Fukada Y,Handa M,Koike T,Ikeda Y: "Erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A,and STAT5B in primary cultured human erythroid precurcers." Blood. 92(2). 443-451 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ozaki K,Oda A,Wakao H,Rhodes J,Druker BJ,Ishida A,Wakui M,Okamoto S,Morita K,Handa M,Komatsu N,Ohashi H,Miyajima A,Ikeda Y: "Thrombopoietin Induces Associationof Crkl with STAT5 but not with STAT3 in human platelets." Blood. 92(12). 4652-4662 (1998)
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「研究成果報告書概要(欧文)」より
