Phosphorylation of c-jun mediated by MAP kinases.
The proto-oncogene c-jun is a component of the AP-1 transcription factor family involved in the mediation of nuclear events elicited by extracellular stimuli. The c-jun protein is negatively regulated by phosphorylation of residues near the carboxy terminus which are dephosphorylated in response to phorbol esters. Here we identify two serine residues in the amino terminal A1 transactivation domain which are phosphorylated in response to a variety of mitogens, phorbol esters and activated ras. We present evidence that mitogen-activated protein-serine (MAP) kinases (pp54 and pp42/44) specifically phosphorylate these sites and that their phosphorylation positively regulates the transacting activity of c-jun. The MAP kinase enzymes pp54 and pp42/44 are regulated by tyrosine as well as serine/threonine phosphorylation. MAP kinase activation of c-jun may underlie the common stimulation of this transcription factor by mitogens, growth factors and oncogenes.
Ludwig Institute for Cancer Research, London, UK.
B J
BJ
Pulverer
J M
JM
Kyriakis
J
J
Avruch
E
E
Nikolakaki
J R
JR
Woodgett
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006801:Humans; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015533:Transcriptional Activation; D014162:Transfection; D014357:Trypsin
C000715470:MAS1 protein, human; D010446:Peptide Fragments; D010703:Phorbol Esters; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D010768:Phosphoserine; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D014357:Trypsin