Regulation of Ferritin mRNA Translation in Primary Erythroblasts: Exogenous c-Kit plus EpoR Signaling Mimics v-ErbA Oncoprotein Activity

• Published in: Biochemical and biophysical research communications Vol. 275; no. 2; pp. 292 - 294
• Main Authors: Mikulits, Wolfgang, Schranzhofer, Matthias, Deiner, Eva Maria, Beug, Hartmut, Müllner, Ernst W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.08.2000
• Subjects: Animals; c-Kit; c-Kit protein; Cells, Cultured; Chickens; Erythroblasts - drug effects; Erythroblasts - metabolism; erythropoietin receptor; erythropoietin receptors; ferritin H chain mRNA; Ferritins - genetics; Oncogene Proteins v-erbA - metabolism; Protein Biosynthesis; Proto-Oncogene Proteins c-kit - pharmacology; Receptors, Erythropoietin - metabolism; RNA, Messenger - genetics; Signal Transduction; translational control; v-ErbA oncoprotein; v-ErbA protein; erythropoietin receptor; translational control; c-Kit; v-ErbA oncoprotein; ferritin H chain mRNA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3300

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.