Mitogenic signals control translation of the early growth response gene-1 in myogenic cells.
Muscle is a major site of expression of the early growth response gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle Sol8 cells. Three groups of responses could be distinguished: 1. AII, endothelin, phenylephrine, and PMA induced Egr-1 mRNA accumulation, but the message remained untranslated. These factors induced neither differentiation nor proliferation. 2. Insulin induced differentiation. It stimulated Egr-1 mRNA accumulation, but no translation into the Egr-1 protein was seen. 3. bFGF, PDGF BB, and FCS strongly induced DNA- and protein synthesis (i.e. proliferation) and Egr-1 mRNA accumulation. Only under these conditions was the message translated into protein. We conclude: 1. AII, endothelin, phenylephrine, and PMA elicit a nuclear response in Sol8 muscle cells which may lead to reprogramming of genes unrelated to differentiation or proliferation. 2. Differentiation induces a translational block of the Egr-1 mRNA which is only relieved by mitotic stimuli. 3. These results strongly suggest a pivotal role of Egr-1 in muscle proliferation and define translational control as a new mechanism of Egr-1 regulation.
Maass
A
A
Medical Policlinic, University of Bonn, FRG.
Grohé
C
C
Oberdorf
S
S
Sukhatme
V P
VP
Vetter
H
H
Neyses
L
L
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D016232:Endothelins / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D017874:Immediate-Early Proteins; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010656:Phenylephrine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D014176:Protein Biosynthesis; D020574:Proto-Oncogene Proteins c-sis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016232:Endothelins; D017874:Immediate-Early Proteins; D007328:Insulin; D009838:Oligodeoxyribonucleotides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D000077214:Becaplermin; D010656:Phenylephrine; D013755:Tetradecanoylphorbol Acetate