NEURITE OUTGROWTH OF PC12 CELLS IS SUPPRESSED BY WORTMANNIN, A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE

The effects of wortmannin (WT), an inhibitor of phosphatidylinositol ( PI) 3-kinase, on differentiation of PC12 cells were analyzed. WT inhib ited PI 3-kinase activity of PC12 cells at a concentration of 10(-7) M in vivo and in vitro. Transient inhibition of PI 3-kinase activity at the time of nerve growth factor stimulation had no effect on activati on of the ras protein or neurite formation by the cells. However, cont inuous inhibition of PI 3-kinase blocked differentiation at the step j ust before neurite formation. When WT was applied to cells growing neu rites, elongation of the neurites was stopped at that step. These resu lts suggest that PI 3-kinase may be involved in neurite elongation.