PMID- 10066421 OWN - NLM STAT- MEDLINE DCOM- 19990413 LR - 20211203 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 256 IP - 1 DP - 1999 Mar 5 TI - Inactivation of mitogen-activated protein kinases by a mammalian tyrosine-specific phosphatase, PTPBR7. PG - 52-6 AB - Mitogen-activated protein kinase (MAPK) is inactivated through dephosphorylation of tyrosyl and threonyl regulatory sites. In yeast, both dual-specificity and tyrosine-specific phosphatases are involved in dephosphorylation. In mammals, however, no tyrosine-specific phosphatase has been identified molecularly to dephosphorylate MAPK in vivo. Recently, we and others have cloned a murine tyrosine-specific phosphatase, PTPBR7/PTP-SL, which is expressed predominantly in the brain. Here we report inactivation of the extracellular signal-regulated kinase (ERK) family MAPK by PTPBR7. PTPBR7 made complexes with ERK1/ERK2 in vivo and dephosphorylated ERK1 in vitro. When overexpressed in mammalian cells, wild-type PTPBR7 suppressed the phosphorylation and activation of ERK by epidermal growth factor (EGF), nerve growth factor (NGF), and constitutively active MEK1, a mutant MAPK kinase. In contrast, catalytically inactive and ERK-binding-deficient mutants revealed little inhibition on the ERK cascade. These results indicate that PTPBR7 suppresses MAPK directly in vivo. CI - Copyright 1999 Academic Press. FAU - Ogata, M AU - Ogata M AD - Biomedical Research Center, Osaka University Medical School C6, 2-2 Yamadaoka, Osaka, Suita, 565-0871, Japan. mogata@ongene.med.osaka-u.ac.jp FAU - Oh-hora, M AU - Oh-hora M FAU - Kosugi, A AU - Kosugi A FAU - Hamaoka, T AU - Hamaoka T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Isoenzymes) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 1) RN - EC 2.7.12.2 (MAP2K1 protein, human) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.1.3.48 (PTPRR protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (Ptprr protein, rat) RN - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 7) SB - IM MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/genetics/metabolism MH - Catalytic Domain/genetics MH - Cell Line MH - Cell Membrane/enzymology MH - Cytosol/enzymology MH - Enzyme Activation/drug effects MH - Epidermal Growth Factor/pharmacology MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Isoenzymes/genetics/metabolism MH - MAP Kinase Kinase 1 MH - *Mitogen-Activated Protein Kinase Kinases MH - Mutation MH - Nerve Growth Factors/pharmacology MH - Nerve Tissue Proteins/genetics/*metabolism MH - PC12 Cells MH - Phosphorylation/drug effects MH - Precipitin Tests MH - Protein Binding MH - Protein Serine-Threonine Kinases/genetics/metabolism MH - Protein Tyrosine Phosphatases/genetics/*metabolism MH - Protein-Tyrosine Kinases/genetics/metabolism MH - Rats MH - Receptor-Like Protein Tyrosine Phosphatases, Class 7 MH - Recombinant Fusion Proteins/metabolism MH - Transfection MH - Yeasts/genetics/metabolism EDAT- 1999/03/06 00:00 MHDA- 1999/03/06 00:01 CRDT- 1999/03/06 00:00 PHST- 1999/03/06 00:00 [pubmed] PHST- 1999/03/06 00:01 [medline] PHST- 1999/03/06 00:00 [entrez] AID - S0006-291X(99)90278-4 [pii] AID - 10.1006/bbrc.1999.0278 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1999 Mar 5;256(1):52-6. doi: 10.1006/bbrc.1999.0278.