1994 Fiscal Year Final Research Report Summary
Structure and Signal Transduction of the Erythropoietin Receptor
| Project/Area Number |
05680618
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cell biology
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| Research Institution | Cancer Research Institute, Faculty of Medicine, Kagoshima University |
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Principal Investigator |
YOSHIMURA Akihiko Cancer Research Institute, Faculty of Medicine, Kagoshima University, 医学部, 助教授 (90182815)
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| Co-Investigator(Kenkyū-buntansha) |
HARAGUCHI Misako Cancer Research Institute, Faculty of Medicine, Kagoshima University, 医学部, 助手 (10244229)
SUMIZAWA Tomoyuki Cancer Research Institute, Faculty of Medicine, Kagoshima University, 医学部, 助手 (90206582)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Erythropoietin / Epidermal growth factor / Dimerization / Activation / SH2 domain / Tyrosine kinase / シグナル伝達 |
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| Research Abstract |
Interaction of erythropoietin (EPO) and its memebrane receptor induces the proliferation and differentiation of erythroid progenitors. The molecular mechanism of the EPO receptor-mediated signal transduction remains unclear because the cloned EPO receptor does not contain any enzyme-related or nucleotide-binding consensus sequences in its cytoplasmic domain. We have shown that chimeric receptors carrying the extracellular domain of the EGF receptor linked to the cytoplasmic domain of the EPO receptor can transmit EGF dependent-proliferation signals in an interleukin-3 dependent Ba/F3 cell line, supporting the hyphothesis that the EPOR is activated by receptor dimerization. We also showed that these chimeric receptors can transmit erythroid differentiation signals in an EPO-responsive erythroleukemia cell line, TSA8. EGF as well as EPO induced globin and hemoglobin synthesis in TSA8 cells expressing the chimeric receptor. A chimeric receptor carring the extracellular domain of the EGF receptor and the membrane proximal about 120 amino acids of the cytoplasmic domain of the EPOR can also transmit proliferation in Ba/F3 cells and differentiation signals in TSA8 cells. These data indicate that a membrane proximal region the cytoplasmic domain of the EPOR is sufficient to produce both proliferation and differentiation signals if it is properly activated by dimerization. We isolated and EPO-induced immediate early gene, CIS which contains SH2 domain. Mechanism of the induction by EPO and function of CIS is now under investigation.
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