title: GATA-dependent regulation of TPO-induced c-mpl gene expression during megakaryopoiesis.
abstract: Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to examine participating possibility of GATA promoter element in TPO- induced c-mpl gene expression through a PKC-independent pathway, the promoter activity of site-directed mutagenesis and the effect of potein kinase C modulator were measured by a transient transfection assay system. Together with our previous results on the TPO-induced c-mpl promoter, this study indicates destruction of -77GATA in c-mpl promoter decreased the activity by 47.3% under existence of GF109203. These results suggest that GATA promoter element plays significant role in TPO-induced c-mpl gene expression through a PKC-independent pathway.
authors.affiliation: Department of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sunohara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Fuse
authors.forename: Iwao
authors.initials: I
authors.lastname: Sato
mesh_terms: D045744:Cell Line, Tumor; D050980:GATA Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D055016:Megakaryocyte Progenitor Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D053628:Receptors, Thrombopoietin / Q000378:metabolism*; D013926:Thrombopoietin / Q000378:metabolism*
chemical_list: D050980:GATA Transcription Factors; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin