Regulation of ferritin mRNA translation in primary erythroblasts: exogenous c-Kit plus EpoR signaling mimics v-ErbA oncoprotein activity.
In general, translation efficiency of ferritin mRNAs is modulated by variations in iron supply. In primary avian erythroblasts undergoing short-term proliferation, however, ferritin heavy chain (ferH) mRNA is repressed at all iron levels. Yet, expression of v-ErbA oncoprotein is sufficient to reinduce ferH mRNA utilization at physiological iron concentrations. Since overexpression of the receptor tyrosine kinase c-Kit and erythropoietin receptor (EpoR) stimulates long-term proliferation of primary erythroblasts like v-ErbA, we analyzed the impact of cooperation between c-Kit and EpoR on the regulation of iron storage. Whereas endogenous c-Kit in combination with exogenous EpoR had no significant effect, ectopic overexpression of both receptors abolished translational repression of ferH mRNA upon iron administration. Thus, high-intensity signaling through c-Kit plus EpoR pathways mimics the v-ErbA-mediated regulatory phenotype.
Mikulits
W
W
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria.
Schranzhofer
M
M
Deiner
E M
EM
Beug
H
H
Müllner
E W
EW
D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D004900:Erythroblasts / Q000187:drug effects / Q000378:metabolism*; D005293:Ferritins / Q000235:genetics*; D018774:Oncogene Proteins v-erbA / Q000378:metabolism*; D014176:Protein Biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015398:Signal Transduction
D018774:Oncogene Proteins v-erbA; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D005293:Ferritins; D019009:Proto-Oncogene Proteins c-kit