Neurochemical Research

, Volume 34, Issue 6, pp 1101–1112 | Cite as

Multiple Gi Proteins Participate in Nerve Growth Factor-Induced Activation of c-Jun N-terminal Kinases in PC12 Cells

  • Prudence H. Tso
  • Christina J. Morris
  • Lisa Y. Yung
  • Nancy Y. Ip
  • Yung H. Wong
ORIGINAL PAPER

Abstract

Nerve growth factor (NGF)-mediated activation of mitogen-activated protein kinases (MAPK) is critical for differentiation and apoptosis of PC12 cells. Since NGF employs stress-activated c-Jun N-terminal kinase (JNK) to regulate both programmed cell death and neurite outgrowth of PC12 cells, we examined NGF-regulated JNK activity and the role of Gi/o proteins. Induction of JNK phosphorylation by NGF occurred in a time- and dose-dependent manner and was partially inhibited by pertussis toxin (PTX). To discern the participation of various signaling intermediates, PC12 cells were treated with specific inhibitors prior to NGF challenge. NGF-elevated JNK activity was abolished by inhibitors of JNK, p38 MAPK, Src, JAK3 and MEK1/2. NGF-dependent JNK phosphorylation became insensitive to PTX treatment upon transient expressions of Gαz or the PTX-resistant mutants of Gαi1–3 and GαoA. Collectively, these studies indicate that NGF-dependent JNK activity may be mediated via Gi1–3 proteins, JAK3, Src, p38 MAPK and the MEK/ERK cascade.

Keywords

Nerve growth factor c-Jun N-terminal kinase Gi/o proteins PC12 pheochromocytoma cells Neurite outgrowth Trk-A receptor 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Prudence H. Tso
    • 1
  • Christina J. Morris
    • 1
  • Lisa Y. Yung
    • 1
  • Nancy Y. Ip
    • 1
  • Yung H. Wong
    • 1
  1. 1.Department of Biochemistry, The Molecular Neuroscience Center, The Biotechnology Research InstituteHong Kong University of Science and TechnologyKowloonHong Kong, China

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