Zn2+ induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase

Soo Jung Eom, Eun Young Kim, Ji Eun Lee, Hyo Jung Kang, Jaekyung Shim, Seong Up Kim, Byoung Joo Gwag, Eui Ju Choi

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Zn2+, one of the most abundant trace metal ions in mammalian cells, modulates the functions of many regulatory proteins associated with a variety of cellular activities. In the central nervous system, Zn2+ is highly localized in the cerebral cortex and hippocampus. It has been proposed to play a role in normal brain function as well as in the pathophysiology of certain neurodegenerative disorders. We here report that Zn2+ induced stimulation of the c-Jun N-terminal kinase (JNK) pathway in mouse primary cortical cells and in various cell lines. Exposure of cells to Zn2+ resulted in the stimulation of JNK and its upstream kinases including stress-activated protein kinase kinase and mitogen-activated protein kinase kinase kinase. Zn2+ also induced stimulation of phosphoinositide 3-kinase (PI3K). The Zn2+-induced JNK stimulation was blocked by LY294002, a PI3K inhibitor, or by a dominant-negative mutant of PI3Kγ. Furthermore, overexpression of Rac1N17, a dominant negative mutant of Rac1, suppressed the Zn2+- and PI3Kγ-induced JNK stimulation. The stimulatory effect of Zn2+ on both PI3K and JNK was repressed by the free-radical scavenging agent N-acetylcysteine. Taken together, our data suggest that Zn2+ induces stimulation of the JNK signaling pathway through PI3K-Rac1 signals and that the free-radical generation may be an important step in the Zn2+ induction of the JNK stimulation.

Original languageEnglish
Pages (from-to)981-986
Number of pages6
JournalMolecular Pharmacology
Volume59
Issue number5
Publication statusPublished - 2001 May 9

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1-Phosphatidylinositol 4-Kinase
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
Free Radicals
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Acetylcysteine
Heat-Shock Proteins
Neurodegenerative Diseases
Cerebral Cortex
Protein Kinases
Hippocampus
Phosphotransferases
Central Nervous System
Metals
Ions
Cell Line
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Eom, S. J., Kim, E. Y., Lee, J. E., Kang, H. J., Shim, J., Kim, S. U., ... Choi, E. J. (2001). Zn2+ induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase. Molecular Pharmacology, 59(5), 981-986.

Zn2+ induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase. / Eom, Soo Jung; Kim, Eun Young; Lee, Ji Eun; Kang, Hyo Jung; Shim, Jaekyung; Kim, Seong Up; Gwag, Byoung Joo; Choi, Eui Ju.

In: Molecular Pharmacology, Vol. 59, No. 5, 09.05.2001, p. 981-986.

Research output: Contribution to journalArticle

Eom, SJ, Kim, EY, Lee, JE, Kang, HJ, Shim, J, Kim, SU, Gwag, BJ & Choi, EJ 2001, 'Zn2+ induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase', Molecular Pharmacology, vol. 59, no. 5, pp. 981-986.
Eom, Soo Jung ; Kim, Eun Young ; Lee, Ji Eun ; Kang, Hyo Jung ; Shim, Jaekyung ; Kim, Seong Up ; Gwag, Byoung Joo ; Choi, Eui Ju. / Zn2+ induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-kinase. In: Molecular Pharmacology. 2001 ; Vol. 59, No. 5. pp. 981-986.
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