Protein serine/threonine phosphatase Ptc2p negatively regulates the unfolded-protein response by dephosphorylating Ire1p kinase.

Molecular and Cellular Biology
A A WelihindaR J Kaufman

Abstract

Cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing the transcription of the genes encoding ER-resident chaperone proteins. Ire1p is a transmembrane protein kinase that transmits the signal from unfolded proteins in the lumen of the ER by a mechanism that requires oligomerization and trans-autophosphorylation of its cytoplasmic-nucleoplasmic kinase domain. Activation of Ire1p induces a novel spliced form of HAC1 mRNA that produces Hac1p, a transcription factor that is required for activation of the transcription of genes under the control of the unfolded-protein response (UPR) element. Searching for proteins that interact with Ire1p in Saccharomyces cerevisiae, we isolated PTC2, which encodes a serine/threonine phosphatase of type 2C. The Ptc2p interaction with Ire1p is specific, direct, dependent on Ire1p phosphorylation, and mediated through a kinase interaction domain within Ptc2p. Ptc2p dephosphorylates Ire1p efficiently in an Mg2+-dependent manner in vitro. PTC2 is nonessential for growth and negatively regulates the UPR pathway. Strains carrying null alleles of PTC2 have a three- to fourfold-increased UPR and increased levels of spliced HAC1 mRNA. Overexpression of wild-t...Continue Reading

References

Jan 2, 1992·Nature·M J Gething, J Sambrook
May 25, 1990·Nucleic Acids Research·M E SchmittB L Trumpower
Jan 1, 1988·Methods in Enzymology·S TsuikiS Tamura
Dec 1, 1986·Mutation Research·G DasF Sherman
Aug 1, 1996·Trends in Biochemical Sciences·M C Faux, J D Scott
Nov 1, 1996·Trends in Biochemical Sciences·D Barford

❮ Previous
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Citations

Dec 11, 2007·Critical Reviews in Biochemistry and Molecular Biology·Twan Lammers, Sara Lavi
Jan 13, 2009·Biochemical and Biophysical Research Communications·Atsushi NagaiHidenori Ichijo
Jul 17, 2003·Molecular Microbiology·Martin SchröderRandal J Kaufman
Dec 18, 2004·Mutation Research·Martin Schröder, Randal J Kaufman
Sep 15, 2004·Journal of Chemical Neuroanatomy·Xiaohua ShenRandal J Kaufman
Apr 2, 2003·Molecular Cell·Christophe LeroyMarie-Claude Marsolier-Kergoat
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Heather P HardingDavid Ron
Sep 1, 2012·Annual Review of Genetics·Kristin A Moore, Julie Hollien
Jun 15, 2005·Annual Review of Biochemistry·Martin Schröder, Randal J Kaufman
Jan 19, 1999·Annual Review of Cell and Developmental Biology·R ChapmanP Walter
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Haiyuan Yu, Mark Gerstein
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·K MoriT Yura
Nov 23, 2006·Current Genetics·Jasmine GrinyerHelena Nevalainen
Feb 2, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Donald J DeGraciaBlaine C White
Apr 18, 2013·International Journal of Molecular Sciences·Yan DengStephen H Howell
Aug 6, 1999·Molecular Biology of the Cell·F Gaits, P Russell
Jan 6, 2012·Molecular Biology of the Cell·Patrick LajoieErik L Snapp
Dec 22, 2004·Nature Immunology·Joseph W Brewer, Linda M Hendershot
Nov 6, 2007·Antioxidants & Redox Signaling·Hiderou Yoshida
Sep 22, 2007·Antioxidants & Redox Signaling·Margaret M Kincaid, Antony A Cooper
Jan 7, 2003·The Journal of Biological Chemistry·Paula OfekSara Lavi
Jul 18, 2003·Yeast·Vanessa M Runner, Jay L Brewster
Jun 1, 2017·Molecular and Cellular Biology·Michael C ArmstrongMartin Schröder
Nov 16, 2010·Eukaryotic Cell·Joaquín AriñoAsier González
Jan 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Gonen MemisogluJames E Haber
Jan 7, 2006·Cell Death and Differentiation·J Wu, R J Kaufman

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