Nerve growth factor induces protein-tyrosine phosphorylation.

When the sympathetic nerve-like cell line PC12 is exposed to nerve growth factor (NGF), there is a rapid and transient phosphorylation of tyrosine residues in cellular proteins, as demonstrated by immunoblotting of cell extracts with high-affinity polyclonal antibodies specific for phosphotyrosine residues. Epidermal growth factor (EGF), which does not cause the morphological differentiation of PC12 cells that is produced by NGF, also induces protein-tyrosine phosphorylation. The methyltransferase inhibitor, 5'-methylthioadenosine, which is known to block the NGF-mediated morphological differentiation of PC12 cells, also inhibits the induction of protein-tyrosine phosphorylation by NGF. 5'-Methylthioadenosine has no effect, however, on EGF-stimulated phosphorylation of tyrosine residues in cellular proteins. In addition, low temperature markedly slows the rate of protein-tyrosine phosphorylation stimulated by NGF, but it has no effect on the time course of protein-tyrosine phosphorylation induced by EGF. These data suggest that NGF and EGF induce protein-tyrosine phosphorylation in PC12 cells by different mechanisms.