Induction of erythroid-specific gene expression in lymphoid cells.
Erythropoietin (Epo) is a cytokine which specifically regulates differentiation and proliferation of erythroid progenitor cells. We report here that Epo receptor expressed in interleukin 3-dependent lymphoid Ba/F3 cells transmits both differentiation and growth signals. Epo stimulation of these cells leads to activation of transcription and/or translation of the erythroid-specific transcription factors GATA-1 and SCL, followed by the accumulation of both alpha- and beta-globin chains. These results suggest that expression and activation of the Epo receptor regulates erythroid-specific gene expression and might play a role in determining a cell lineage in vivo and that GATA-1 and SCL may exert their effects after Epo binds to its receptor. It was further found that chimeric receptors composed of extracellular domains of Epo receptor and cytoplasmic domains of interleukin 2 or interleukin 3 receptors could also induce erythroid-specific gene expression in Ba/F3 cells. Taking these data together with previous observations, we conclude that interaction of the extracellular domains of the Epo receptor with other membrane components is essential for transmission of both the erythroid differentiation and the growth signals.
Chiba
T
T
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nagata
Y
Y
Kishi
A
A
Sakamaki
K
K
Miyajima
A
A
Yamamoto
M
M
Engel
J D
JD
Todokoro
K
K
D000818:Animals; D001402:B-Lymphocytes; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000494:pharmacology; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005914:Globins / Q000096:biosynthesis; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin; D050982:GATA1 Transcription Factor; D005914:Globins; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human