Identification of a nerve growth factor- and epidermal growth factor-regulated protein kinase that phosphorylates the protooncogene product c-Fos.
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.
Taylor
L K
LK
Department of Neurosciences, Alzheimer Research Laboratory, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Marshak
D R
DR
Landreth
G E
GE
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
D008024:Ligands; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D012694:Serine; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa