Abstract
MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N nor c-Jun amino-terminal kinase-stress-activated protein kinase (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation. These kinases were also resistant to enzymatic inactivation by MKP-3. Another homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2, JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems.
MeSH terms
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Amino Acid Sequence
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Animals
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Catalysis
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Dual Specificity Phosphatase 6
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Enzyme Activation
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Epidermal Growth Factor / pharmacology
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Mutation
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Phosphorylation
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Protein Kinases / metabolism
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Transfection
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p38 Mitogen-Activated Protein Kinases
Substances
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Recombinant Fusion Proteins
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Epidermal Growth Factor
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Protein Kinases
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinase 9
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Dual Specificity Phosphatase 6
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Protein Tyrosine Phosphatases