Journal Article

Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase

Camps, Montserrat, Nichols, Anthony, Arkinstall, Steve, Antonsson, Bruno, Gillieron, Corine, Muda, Marco, Chabert, Christian, Boschert, Ursula

1998

Overview

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.

• Publisher: American Society for the Advancement of Science,American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Amino Acid Sequence / Amino acids / Animals / Biological and medical sciences / Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors / Calcium-Calmodulin-Dependent Protein Kinases - genetics / Calcium-Calmodulin-Dependent Protein Kinases - metabolism / Catalysis / Cell physiology / Cell receptors / Cellular signal transduction / COS Cells / Dual Specificity Phosphatase 6 / Enzyme Activation / Enzymes / Epidermal Growth Factor - pharmacology / Fundamental and applied biological sciences. Psychology / Genetic mapping / Hydrolysis / Immunoblotting / Inactivation / Individualized Instruction / Inhibition / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 12 / Mitogen-Activated Protein Kinase 9 / Mitogen-Activated Protein Kinases / Molecular and cellular biology / Molecular Sequence Data / Mutation / p38 Mitogen-Activated Protein Kinases / Pharmacology / Phosphatases / Phosphorylation / Plasmids / Protein Kinases - metabolism / Protein Tyrosine Phosphatases - genetics / Protein Tyrosine Phosphatases - metabolism / Proteins / Recombinant Fusion Proteins - metabolism / Signal Transduction / Transfection