Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase.

The Journal of Biological Chemistry
K L Guan, E Butch

Abstract

The mitogen-activated protein kinase (MAPK) also known as extracellular signal-regulated kinase (ERK) plays a crucial role in various signal transduction pathways. ERK is activated by its upstream activator, MEK, via threonine and tyrosine phosphorylation. ERK activity in the cell is tightly regulated by phosphorylation and dephosphorylation. Here we report the cloning and characterization of a novel dual specific phosphatase, HVH2, which may function in vivo as a MAP kinase phosphatase. The deduced amino acid sequence of HVH2 shows significant identity to the VH1-related dual specific phosphatase family. In addition, the N-terminal region of HVH2 also displays sequence identity to the cell cycle regulator, Cdc25 phosphatase. Recombinant HVH2 phosphatase exhibited a high substrate specificity toward activated ERK and dephosphorylated both threonine and tyrosine residues of activated ERK1 and ERK2. Immunofluorescence studies with an epitope-tagged HVH2 showed that the enzyme was localized in cell nucleus. Transfection of HVH2 into NIH3T3 cells inhibited the v-src and MEK-induced transcriptional activation of serum-responsive element containing promoter, consistent with the notion that HVH2 promotes the inactivation of MAP kinase...Continue Reading

References

Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T IshibashiS A Aaronson
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·K GuanJ E Dixon
Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J W HaycockE G Krebs
Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A J RossomandoT W Sturgill
Sep 4, 1992·Science·S L Pelech, J S Sanghera
Jan 1, 1992·Methods in Enzymology·B R Cullen, M H Malim
Mar 1, 1992·Molecular and Cellular Biology·R H ChenJ Blenis
Jul 13, 1992·FEBS Letters·T A HaysteadT W Sturgill
Dec 1, 1991·Trends in Biochemical Sciences·C Dingwall, R A Laskey
Dec 1, 1991·Cell Regulation·M H CobbD J Robbins
Mar 28, 1991·Nature·K L GuanJ E Dixon
Oct 17, 1991·Nature·B J PulvererJ R Woodgett
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R JanknechtH G Stunnenberg
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K L GuanJ E Dixon
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L B Ray, T W Sturgill
Dec 1, 1985·Molecular and Cellular Biology·G I EvanJ M Bishop
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J HannonD Beach
Oct 1, 1993·Trends in Biochemical Sciences·S M Keyse, M Ginsburg
Dec 1, 1993·Seminars in Cell Biology·K L Guan, J E Dixon
Jan 29, 1993·Cell·L L LinR J Davis
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C H CharlesN K Tonks
Apr 1, 1993·Current Opinion in Cell Biology·B Errede, D E Levin

❮ Previous
Next ❯

Citations

Jul 8, 1999·Journal of Cellular Physiology·J Chernoff
Mar 29, 2000·Biochemical and Biophysical Research Communications·R ZhaoZ J Zhao
Dec 1, 1995·Current Opinion in Cell Biology·A J Waskiewicz, J A Cooper
Apr 30, 2004·Cellular Signalling·Amjad Farooq, Ming-Ming Zhou
May 29, 1998·Brain Research. Molecular Brain Research·P Peinado-RamónF Hallböök
Feb 13, 2001·Molecular and Cellular Endocrinology·T ZhangM S Roberson
Jan 3, 2003·Mutation Research·Jun YangPenelope J Duerksen-Hughes
May 3, 2007·Nature Reviews. Drug Discovery·Kate L JeffreyCharles R Mackay
Feb 24, 2007·Nature Reviews. Immunology·Yusen LiuLeif D Nelin
Mar 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Mingcan YuJörg J Goronzy
May 12, 2000·Critical Care Medicine·T ObataM B Yaffe
May 16, 2013·Science Signaling·Xun LiMaja Köhn
Mar 31, 2010·Infection and Immunity·Timothy T CornellThomas P Shanley
Sep 25, 2003·Annual Review of Plant Biology·Sheng Luan
Jun 12, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Timothy T CornellThomas P Shanley
Jan 13, 2011·Physiological Genomics·Zhaoyang ZhaoCheng Chi Lee
Oct 1, 1996·The Journal of Clinical Investigation·K LaiE Haber
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·M KanaiD K Podolsky
Jun 15, 2012·Cellular and Molecular Life Sciences : CMLS·Ahmed LawanAnton M Bennett
May 1, 1996·Kidney International·D BokemeyerM J Dunn
Jan 21, 2012·Biochemical Society Transactions·Ahmed LawanRobin Plevin
Oct 13, 2007·Osteoarthritis and Cartilage·K JaegerB Mueller-Hilke
Mar 4, 2015·Blood·Alexandre BignonKarl Balabanian

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.