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Mitogenic signals control translation of the early growth response gene-1 in myogenic cells
1Medical Policlinic, University of Bonn, FRG.
Abstract:
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.
Insights
Growth factors differentially regulate early growth response gene-1 (Egr-1) in muscle cells. Egr-1 translation is linked to proliferation, not differentiation, revealing a novel regulatory mechanism.
Area of Science:
- Molecular Biology
- Cell Biology
- Muscle Physiology
Background:
- Muscle cells express the early growth response gene-1 (Egr-1).
- The precise role of Egr-1 in muscle cell proliferation and differentiation remains unclear.
Purpose of the Study:
- To investigate the role of Egr-1 in muscle cell proliferation and differentiation.
- To determine how various growth factors influence Egr-1 expression and activity in cultured mouse muscle cells (Sol8).
Main Methods:
- Cultured mouse muscle Sol8 cells were treated with various growth factors (AII, endothelin, phenylephrine, PMA, insulin, bFGF, PDGF BB, FCS).
- Egr-1 mRNA accumulation and translation into protein were analyzed.
- Cell proliferation and differentiation were assessed.
Main Results:
- Certain factors (AII, endothelin, phenylephrine, PMA) induced Egr-1 mRNA but not protein, without affecting proliferation or differentiation.
- Insulin induced differentiation and Egr-1 mRNA accumulation, but translation was blocked.
- Growth factors promoting proliferation (bFGF, PDGF BB, FCS) strongly induced Egr-1 mRNA and its translation into protein.
Conclusions:
- Egr-1 plays a pivotal role in muscle cell proliferation.
- Translational control is a key mechanism regulating Egr-1 activity in muscle cells.
- Specific growth factors trigger distinct cellular responses involving Egr-1 regulation.