Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2 / metabolism*
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Animals
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Cell Nucleus / drug effects
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Cell Nucleus / enzymology*
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / enzymology*
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases / deficiency*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mice
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation / drug effects
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Phosphothreonine / metabolism*
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Protein Transport / drug effects
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Pyridines / pharmacology
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Serum
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Signal Transduction / drug effects
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Activating Transcription Factor 2
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Atf2 protein, mouse
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Imidazoles
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Pyridines
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Phosphothreonine
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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SB 203580