Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation

When expressed in PC12 cells, the platelet-derived growth factor β receptor (βPDGF-R) mediates cell differentiation. Mutational analysis of the βPDGF-R indicated that persistent receptor stimulation of the Ras/Raf/mitogen-activated protein (MAP) kinase pathway alone was insufficient to sustain PC12 cell differentiation. PDGF receptor activation of signal pathways involving p60(c-src) or the persistent regulation of phospholipase Cγ was required for PC12 cell differentiation. βPDGF-R regulation of phosphatidylinositol 3-kinase, the GTPase-activating protein of Ras, and the tyrosine phosphatase, Syp, was not required for PC12 cell differentiation. In contrast to overexpression of oncoproteins involved in regulating the MAP kinase pathway, growth factor receptor-mediated differentiation of PC12 cells requires the integration of other signals with the Ras/Raf/MAP kinase pathway.