Tyrosine kinase activity coupled to the high-affinity nerve growth factor-receptor complex.

Antibodies directed against nerve growth factor (NGF) immunoprecipitate a tyrosine kinase activity from NGF-treated PC12 rat pheochromocytoma cells. Based on several criteria, this activity has been correlated with the high-affinity and not the low-affinity NGF-receptor complex. The in vitro kinase activity and the tyrosine phosphorylation of the high-affinity complex can be blocked by an agent that inhibits NGF (and not epidermal growth factor)-induced tyrosine phosphorylation in PC12 cells, as well as NGF-induced neuronal differentiation of PC12 cells. These observations suggest that the high-affinity NGF-receptor complex is a substrate of tyrosine kinase activity. Phosphorylation reactions by the complex, performed in the absence of added substrate, label a single phosphopeptide of 130-135 kDa. This observation suggests that this phosphopeptide may represent the phosphorylation of the receptor kinase or the phosphorylation of a coimmunoprecipitating substrate, and possible signal-transducing molecule, of the high-affinity NGF-receptor complex.