| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Research Abstract |
We have analyzed the physiological function of GATA-1 factor. We found that GATA-1 gene is activated by erythropoietin (Epo) receptor (EpoR)-mediated signal, and that GATA-1 transactivates EpoR gene expression. Thus, GATA-1 is one of the cell lineage determinants of erythroid cells. EpoR-mediated signal activates transcription and translation of GATA-1 gene, and further stimulate serine/threonine phosphorylation of GATA-1 protein. GATA-1 which is expressed in low level before Epo binds to EpoR seems to be inactive, but the enhanced and phosphorylated GATA-1 protein is active to transactivate globin, EpoR, Hox2 family and SCL gene expression. SCL gene product was also found to transactivate EpoR gene as well as globin genes. Transfection of EpoR gene into IL3-dependent Ba/F3 cells resulted in erythroid phenotypic expression of this lymphoid cells, that is, activation of transcription and translation of GATA-1, SCl and globin genes. Furthermore, chimeric receptors constituted with extracellular domains of EpoR and transmembrane and cytoplasmic domains of IL2 or IL3 receptors could transmit erythroid differentiation signal in Ba/F3 cells, indicating that extracellular domains for EpoR is essential for transmission of differentiation as well as growth signals.
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