Induction of Altered c-src Product during Neural Differentiation of Embryonal Carcinoma Cells

The expression of the cellular src gene product pp60$^{\text{c}-src}$ was examined in an embryonal carcinoma cell line that differentiates in vitro into neuronlike cells after being treated with retinoic acid. Quantitative and qualitative changes in c-src expression accompanied the events associated with neuronal differentiation. The levels of pp60$^{\text{c}-src}$ increased 8- to 20-fold during the period when the cells elaborated neuritic processes and expressed neuron-specific proteins. The electrophoretic mobility of pp60$^{\text{c}-src}$ induced in these cells was retarded in comparison with that in untreated cells or in treated cells before neurite elaboration. The shift in electrophoretic mobility was due to an alteration in the amino terminal 16,000 daltons of pp60$^{\text{c}-src}$ and similar to an alteration of c-src protein found in neural tissues and in pure primary cultures of neuronal cells. These results indicate that expression of pp60$^{\text{c}-src}$ induced by retinoic acid in these embryonal carcinoma cells mimics the expression of c-src in developing neurons. Therefore, this embryonal carcinoma cell line provides a model system to investigate the function of the src protein in neuronal differentiation.