Identification of a Nerve Growth Factor- and Epidermal Growth Factor- Regulated Protein Kinase that Phosphorylates the Protooncogene Product c-Fos

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 2; pp. 368 - 372
• Main Authors: Taylor, Lori K., Marshak, Daniel R., Landreth, Gary E.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.01.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Animals; Biochemistry; Biological and medical sciences; Cell growth; Cell Transformation, Neoplastic; Cellular biology; Chromatography; Depolarization; Enzyme Activation; Enzymes; Enzymes and enzyme inhibitors; epidermal growth factor; Epidermal Growth Factor - pharmacology; Fibroblast Growth Factors - pharmacology; Fos protein; Fundamental and applied biological sciences. Psychology; identification; Ligands; Molecular Sequence Data; nerve growth factor; Nerve Growth Factors - pharmacology; Nerves; Neurology; PC12 Cells; Peptide Fragments - metabolism; Phosphorylation; protein kinase; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-fos - metabolism; rats; regulation; Ribosomal Protein S6 Kinases, 90-kDa; Serine - metabolism; Signal Transduction; Transferases; Phosphorylation; Pheochromocytoma; Purification; Rat; Enzyme; Gene product; Rodentia; Nerve growth factor; Transcription repressor; Vertebrata; Mammalia; Epidermal growth factor; Polypeptide; Protein kinase; C-Onc gene; Protooncogene; Growth factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.2.368

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.