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.