PMID- 15281913 OWN - NLM STAT- MEDLINE DCOM- 20050511 LR - 20191210 IS - 1470-8728 (Electronic) IS - 0264-6021 (Print) IS - 0264-6021 (Linking) VI - 383 IP - Pt. 3 DP - 2004 Nov 1 TI - Characterization of a novel low-molecular-mass dual-specificity phosphatase-3 (LDP-3) that enhances activation of JNK and p38. PG - 447-55 AB - We have isolated a mouse cDNA for a novel dual-specificity phosphatase designated LDP-3 (low-molecular-mass dual-specificity phosphatase 3). The 450 bp open reading frame encodes a protein of 150 amino acids with a predicted molecular mass of 16 kDa. Northern blot and reverse transcription-PCR analyses show that LDP-3 transcripts are expressed in almost all mouse tissues examined. In vitro analyses using several substrates and inhibitors indicate that LDP-3 possesses intrinsic dual-specificity phosphatase activity. When expressed in mammalian cells, LDP-3 protein is localized mainly to the apical submembrane area. Forced expression of LDP-3 does not alter activation of ERK (extracellular-signal-regulated kinase), but rather enhances activation of JNK (c-Jun N-terminal kinase) and p38 and their respective upstream kinases MKK4 (mitogen-activated protein kinase kinase 4) and MKK6 in cells treated with 0.4 M sorbitol. By screening with a variety of stimuli, we found that LDP-3 specifically enhances the osmotic stress-induced activation of JNK and p38. FAU - Takagaki, Kentaro AU - Takagaki K AD - Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan. FAU - Satoh, Takeshi AU - Satoh T FAU - Tanuma, Nobuhiro AU - Tanuma N FAU - Masuda, Kouhei AU - Masuda K FAU - Takekawa, Mutsuhiro AU - Takekawa M FAU - Shima, Hiroshi AU - Shima H FAU - Kikuchi, Kunimi AU - Kikuchi K LA - eng SI - GENBANK/AB164404 SI - GENBANK/AB183013 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 6) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 4) RN - EC 3.1.3.48 (Dual-Specificity Phosphatases) RN - EC 3.1.3.48 (Dusp23 protein, mouse) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Amino Acid Sequence MH - Animals MH - COS Cells/enzymology MH - Cell Line MH - Chlorocebus aethiops MH - Dual-Specificity Phosphatases MH - Enzyme Activation/genetics/physiology MH - Humans MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - MAP Kinase Kinase Kinase 4/metabolism MH - Mice MH - Mitogen-Activated Protein Kinase 6/metabolism MH - Molecular Sequence Data MH - Molecular Weight MH - Mutation/genetics/physiology MH - Osmotic Pressure MH - Protein Tyrosine Phosphatases/*chemistry/genetics/*physiology MH - Substrate Specificity MH - Transfection/methods MH - p38 Mitogen-Activated Protein Kinases/*metabolism PMC - PMC1133737 EDAT- 2004/07/30 05:00 MHDA- 2005/05/12 09:00 PMCR- 2005/05/01 CRDT- 2004/07/30 05:00 PHST- 2004/07/30 05:00 [pubmed] PHST- 2005/05/12 09:00 [medline] PHST- 2004/07/30 05:00 [entrez] PHST- 2005/05/01 00:00 [pmc-release] AID - BJ20040498 [pii] AID - bj3830447 [pii] AID - 10.1042/BJ20040498 [doi] PST - ppublish SO - Biochem J. 2004 Nov 1;383(Pt. 3):447-55. doi: 10.1042/BJ20040498.