Oncogenically activated or ligand-stimulated neu kinase stimulates neurite outgrowth in PC12 cells

Retroviral vectors pDOL/NeuN and pDOL/NeuT were used to express normal and transforming rat neu cDNAs in PC12 cells. DOL/NeuT-infected cells exhibited a high frequency of spontaneous neurite outgrowth while DOL/NeuN-infected cells showed neurite outgrowth in the presence of heregulin, a putative ligand for the neu receptor tyrosine kinase. In both cases, neurite outgrowth was preceded by phosphorylation of p185neu and several other cellular proteins. Thus the neu tyrosine kinase can elicit morphological and biochemical changes resembling, but distinct from, those stimulated by NGF, and heregulin stimulates neu to elicit these effects in PC12 cells.