Nerve Growth Factor Stimulation of the Ras-Guanine Nucleotide Exchange Factor and GAP Activities

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Abstract
The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins.