Signal transduction pathways regulated by arsenate and arsenite

Amy C. Porter, Gary R. Fanger, Richard Vaillancourt

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Arsenate and arsenite activate c-Jun N-terminal kinase (JNK), however, the mechanism by which this occurs is not known. By expressing inhibitory mutant small GTP-binding proteins, p21-activated kinase (PAK) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinases (MEKKs), we have identified specific proteins that are involved in arsenate- and arsenite-mediated activation of JNK. We observe a distinct difference between arsenate and arsenite signaling, which demonstrates that arsenate and arsenite are capable of activating unique proteins. Both arsenate and arsenite activation of JNK requires Rac and Rho. Neither arsenate nor arsenite signaling was inhibited by a dominant-negative mutant of Cdc42 or Ras. Arsenite stimulation of JNK requires PAK, whereas arsenate-mediated activation of JNK was unaffected by inhibitory mutant PAK. Of the four MEKKs tested, only MEKK3 and MEKK4 are involved in arsenate-mediated activation of JNK. In contrast, arsenite-mediated JNK activation requires MEKK2, MEKK3 and MEKK4. These results better define the mechanisms by which arsenate and arsenite activate JNK and demonstrate differences in the regulation of signal transduction pathways by these inorganic arsenic species.

Original languageEnglish (US)
Pages (from-to)7794-7802
Number of pages9
JournalOncogene
Volume18
Issue number54
StatePublished - Dec 16 1999

Fingerprint

JNK Mitogen-Activated Protein Kinases
Signal Transduction
p21-Activated Kinases
MAP Kinase Kinase Kinases
Phosphotransferases
arsenite
arsenic acid
Extracellular Signal-Regulated MAP Kinases
Arsenic
Mitogen-Activated Protein Kinases
GTP-Binding Proteins
Proteins

Keywords

  • Arsenic
  • MEKK3
  • MEKK4
  • PAK
  • Rac
  • Rho

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Signal transduction pathways regulated by arsenate and arsenite. / Porter, Amy C.; Fanger, Gary R.; Vaillancourt, Richard.

In: Oncogene, Vol. 18, No. 54, 16.12.1999, p. 7794-7802.

Research output: Contribution to journalArticle

Porter, AC, Fanger, GR & Vaillancourt, R 1999, 'Signal transduction pathways regulated by arsenate and arsenite', Oncogene, vol. 18, no. 54, pp. 7794-7802.
Porter, Amy C. ; Fanger, Gary R. ; Vaillancourt, Richard. / Signal transduction pathways regulated by arsenate and arsenite. In: Oncogene. 1999 ; Vol. 18, No. 54. pp. 7794-7802.
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