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 beta receptor (beta PDGF-R) mediates cell differentiation. Mutational analy sis of the beta PDGF-R indicated that persistent receptor stimulation of the Ras/Raf/mitogen-activated protein (MAP) kinase pathway alone wa s insufficient to sustain PC12 cell differentiation. PDGF receptor act ivation of signal pathways involving p60(c-src) or the persistent regu lation of phospholipase Cy was required for PC12 cell differentiation. beta PDGF-R regulation of phosphatidylinositol 3-kinase, the GTPase-a ctivating protein of Pas, and the tyrosine phosphatase, Syp, was not r equired for PC12 cell differentiation. In contrast to overexpression o f oncoproteins involved in regulating the MAP kinase pathway, growth f actor receptor-mediated differentiation of PC12 cells requires the int egration of other signals,vith the Ras/Raf/MAP kinase pathway.