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Growth Factor–induced p42/p44 MAPK Nuclear Translocation and Retention Requires Both MAPK Activation and Neosynthesis of Nuclear Anchoring Proteins

Growth Factor–induced p42/p44 MAPK Nuclear Translocation and Retention Requires Both MAPK... Mitogen-activated protein kinases (p42/p44 MAPK, also called Erk2 and Erk1) are key mediators of signal transduction from the cell surface to the nucleus. We have previously shown that the activation of p42/p44 MAPK required for transduction of mitogenic signaling is associated with a rapid nuclear translocation of these kinases. However, the means by which p42 and p44 MAPK translocate into the nucleus after cytoplasmic activation is still not understood and cannot simply be deduced from their protein sequences. In this study, we have demonstrated that activation of the p42/ p44 MAPK pathway was necessary and sufficient for triggering nuclear translocation of p42 and p44 MAPK. First, addition of the MEK inhibitor PD 98059, which blocks activation of the p42/p44 MAPK pathway, impedes the nuclear accumulation, whereas direct activation of the p42/p44 MAPK pathway by the chimera ΔRaf-1:ER is sufficient to promote nuclear accumulation of p42/p44 MAPK. In addition, we have shown that this nuclear accumulation of p42/p44 MAPK required the neosynthesis of short-lived proteins. Indeed, inhibitors of protein synthesis abrogate nuclear accumulation in response to serum and accelerate p42/p44 MAPK nuclear efflux under conditions of persistent p42/p44 MAPK activation. In contrast, inhibition of targeted proteolysis by the proteasome synergistically potentiated p42/p44 MAPK nuclear localization by nonmitogenic agonists and markedly prolonged nuclear localization of p42/p44 MAPK after mitogenic stimulation. We therefore conclude that the MAPK nuclear translocation requires both activation of the p42/p44 MAPK module and neosynthesis of short-lived proteins that we postulate to be nuclear anchors. growth factors signal transduction protein kinases cell compartmentation cell nucleus Footnotes Address all correspondence to Philippe Lenormand, Centre de Biochimie–CNRS UMR 6543, Université de Nice, 06108 Nice, France. Tel.: ( 33 ) 492 07 64 27. Fax: ( 33 ) 492 07 64 32. E-mail: [email protected] Abbreviations used in this paper: CHX cycloheximide ERK extra cellular regulated kinase JNK Jun NH 2 -terminal Kinase LLnL N -Acetyl-Leu-Leu-norLeucinal MAPK mitogen-activated protein kinase MEK MAPK or Erk kinase NLS nuclear localization signal PD 98059 Park Davis 98059 TPA 12- O -tetra decanoyl phorbol myristate acetate Submitted: 24 March 1998 Revision received 8 June 1998 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Growth Factor–induced p42/p44 MAPK Nuclear Translocation and Retention Requires Both MAPK Activation and Neosynthesis of Nuclear Anchoring Proteins

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Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.142.3.625
Publisher site
See Article on Publisher Site

Abstract

Mitogen-activated protein kinases (p42/p44 MAPK, also called Erk2 and Erk1) are key mediators of signal transduction from the cell surface to the nucleus. We have previously shown that the activation of p42/p44 MAPK required for transduction of mitogenic signaling is associated with a rapid nuclear translocation of these kinases. However, the means by which p42 and p44 MAPK translocate into the nucleus after cytoplasmic activation is still not understood and cannot simply be deduced from their protein sequences. In this study, we have demonstrated that activation of the p42/ p44 MAPK pathway was necessary and sufficient for triggering nuclear translocation of p42 and p44 MAPK. First, addition of the MEK inhibitor PD 98059, which blocks activation of the p42/p44 MAPK pathway, impedes the nuclear accumulation, whereas direct activation of the p42/p44 MAPK pathway by the chimera ΔRaf-1:ER is sufficient to promote nuclear accumulation of p42/p44 MAPK. In addition, we have shown that this nuclear accumulation of p42/p44 MAPK required the neosynthesis of short-lived proteins. Indeed, inhibitors of protein synthesis abrogate nuclear accumulation in response to serum and accelerate p42/p44 MAPK nuclear efflux under conditions of persistent p42/p44 MAPK activation. In contrast, inhibition of targeted proteolysis by the proteasome synergistically potentiated p42/p44 MAPK nuclear localization by nonmitogenic agonists and markedly prolonged nuclear localization of p42/p44 MAPK after mitogenic stimulation. We therefore conclude that the MAPK nuclear translocation requires both activation of the p42/p44 MAPK module and neosynthesis of short-lived proteins that we postulate to be nuclear anchors. growth factors signal transduction protein kinases cell compartmentation cell nucleus Footnotes Address all correspondence to Philippe Lenormand, Centre de Biochimie–CNRS UMR 6543, Université de Nice, 06108 Nice, France. Tel.: ( 33 ) 492 07 64 27. Fax: ( 33 ) 492 07 64 32. E-mail: [email protected] Abbreviations used in this paper: CHX cycloheximide ERK extra cellular regulated kinase JNK Jun NH 2 -terminal Kinase LLnL N -Acetyl-Leu-Leu-norLeucinal MAPK mitogen-activated protein kinase MEK MAPK or Erk kinase NLS nuclear localization signal PD 98059 Park Davis 98059 TPA 12- O -tetra decanoyl phorbol myristate acetate Submitted: 24 March 1998 Revision received 8 June 1998

Journal

The Journal of Cell Biology – Rockefeller University Press

Published: Aug 10, 1998

References

  • The mitogen-activated protein kinase activator
    Ahn
  • PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.
    Alessi
  • Signaling in the yeast pheromone response pathway: specific and high- affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7
    Bardwell
  • The proteasome
    Baumeister
  • Reversion of Ras- and phosphatidylcholine-hydrolyzing phospholipase C-mediated transformation of NIH 3T3 cells by a dominant interfering mutant of protein kinase C lambda is accompanied by the loss of constitutive nuclear mitogen-activated protein kinase/extracellular signal-regulated kinase activity
    Bjorkoy
  • ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF
    Boulton
  • The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade
    Brondello
  • Nuclear localization and regulation of ERK- and RSK-encoded protein kinases
    Chen
  • Activation of MAP kinase kinase is both necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells
    Cowley
  • The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product
    Crews
  • Identification and localization of a cysteinyl residue critical for the trypsin-like catalytic activity of the proteasome
    Dick
  • A synthetic inhibitor of the mitogen-activated protein kinase cascade
    Dudley
  • Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin
    Fenteany
  • Cytoplasmic localization of MAP kinase kinase directed by its N-terminal, leucin-rich amino acid sequence, which acts as a nuclear export signal
    Fukuda
  • Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase
    Fukuda
  • Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fospromoter
    Gille
  • ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation
    Gille
  • Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus
    Gonzalez
  • Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase
    Groom
  • Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase
    Guan
  • Transient activation of Raf-1, MEK and ERK2 coincides kinetically with ternary complex factor phosphorylation and immediate-early gene promoter activity in vivo
    Hipskind
  • Nucleotidase activities of the 26 S proteasome and its regulatory complex
    Hoffman
  • Nuclear translocation of mitogen-activated protein kinase kinase (MEK1) in response to mitogenic stimulation
    Jaaro
  • Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells
    Jaffa
  • Sequential protein kinase reactions controlling cell growth and differentiation
    Johnson
  • Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation
    Khokhlatchev
  • Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts
    Lenormand
  • Oncogenic Raf-1 activates p70 S6 kinase via a mitogen-activated protein kinase-independent pathway
    Lenormand
  • The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain
    Marais
  • MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia
    Martin
  • Activation-independent nuclear translocation of mitogen activated protein kinase ERK1 mediated by thiol-modifying chemicals
    Meili
  • Mitogen-activated protein kinase and proliferation of human vascular smooth muscle cells
    Mii
  • Differential activation of ERK and JNK by Raf-1 and MEKK
    Minden
  • A novel mitogen-activated protein kinase phosphatase. Structure, expression, and regulation
    Misra-Press
  • Activation of two isoforms of mitogen-activated protein kinase kinase in response to epidermal growth factor and nerve growth factor
    Moriguchi
  • MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase
    Muda
  • Co-regulation of the mitogen-activated protein kinase, extracellular signal-regulated kinase 1, and the 90-kDa ribosomal S6 kinase in PC12 cells. Distinct effects of the neurotrophic factor, nerve growth factor, and the mitogenic factor, epidermal growth factor
    Nguyen
  • Nucleocytoplasmic transport: signals, mechanisms and regulation
    Nigg
  • Control of gene expression by proteolysis
    Pahl
  • Sequential binding of import ligands to distinct nucleopore regions during their nuclear import
    Pante
  • Mitogen-activated protein kinase pathways
    Robinson
  • Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules
    Rock
  • Inhibition of platelet-derived growth factor- and epidermal growth factor-mediated mitogenesis and signaling in 3T3 cells expressing delta Raf-1:ER, an estradiol-regulated form of Raf-1
    Samuels
  • Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase
    Samuels
  • MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo
    Sun
  • Inhibition of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex
    Vinitsky
  • Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2
    Zheng
  • Cytoplasmic localization of the mitogen-activated protein kinase activator MEK
    Zheng