The nuclear appearance of ERK1/2 and p38 determines the sequential induction of ATF2-Thr71 and ATF2-Thr69 phosphorylation by serum in JNK-deficient cells.
Growth factors activate ATF2 via sequential phosphorylation of Thr69 and Thr71, where the ATF2-Thr71-phosphorylation precedes the induction of ATF2-Thr69+71-phosphorylation. Here, we studied the mechanisms contributing to serum-induced two-step ATF2-phosphorylation in JNK1,2-deficient embryonic fibroblasts. Using anion exchange chromatography, ERK1/2 and p38 were identified as ATF2-kinases in vitro. Inhibitor studies as well as nuclear localization experiments show that the sequential nuclear appearance of ERK1/2 and p38 determines the induction of ATF2-Thr71 and ATF2-Thr69+71-phosphorylation in response to serum.
Baan
Bart
B
Department of Molecular Cell Biology, Section Signal Transduction and Ageing, Leiden University Medical Centre, Postzone S1-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
van der Zon
Gerard C M
GC
Maassen
J Antonie
JA
Ouwens
D Margriet
DM
D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D044967:Serum; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D007093:Imidazoles; D011725:Pyridines; D010769:Phosphothreonine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580