Identification of a nerve growth factor- and epidermal growth factor-regulated protein kinase that phosphorylates the protooncogene product c-Fos.

Abstract

Nerve growth factor (NGF) treatment of rat pheochromocytoma (PC12) cells induces the synthesis of the transcription factor c-Fos, which becomes highly phosphorylated relative to that produced as a result of depolarization of the cell. A peptide derived from the carboxyl terminus of c-Fos (residues 359-370, RKGSSSNEPSSD) containing putative phosphorylation sites was used to detect a NGF-stimulated Fos kinase. NGF treatment of PC12 cells resulted in a rapid activation of a protein kinase which phosphorylated both the c-Fos peptide and authentic c-Fos at its carboxyl terminus. The kinase was selectively activated by NGF and epidermal growth factor but was not induced by depolarization or other agents. The c-Fos peptide was phosphorylated at a serine corresponding to Ser362, a site critically implicated in the capacity of c-Fos to exhibit transrepressive activity [Ofir, R., Dwarki, V. J., Rashid, D. & Verma, I. M. (1990) Nature (London) 348, 80-82)]. The NGF-stimulated Fos kinase may play an important role in regulating the expression and transforming potential of c-Fos.