Please use this identifier to cite or link to this item:

Nerve growth factor-induced stimulation of p38 mitogen-activated protein kinase in PC12 cells is partially mediated via G(i/o) proteins

Authors Yung, Ying
Tso, Ha
Wu, Eddy H.T.
Yu, Jowie C.H.
Ip, Nancy Y.Y.
Wong, Yung Hou
Issue Date 2008
Source Cellular signalling , v. 20, (8), 2008, AUG, p. 1538-1544
Summary Differentiation of PC12 cells by nerve growth factor (NGF) requires the activation of various mitogen-activated protein kinases (MAPKs) including p38 MAPK. Accumulating evidence has suggested cross-talk regulation of NGF-induced responses by G protein-coupled receptors, thus we examined whether NGF utilizes G(i/o) proteins to regulate p38 MAPK in PC12 cells. Induction of p38 MAPK phosphorylation by NGF occurred in a time- and dose-dependent manner and was partially inhibited by pertussis toxin (PTX). NGF-dependent p38 MAPK phosphorylation became insensitive to PTX treatment upon transient expressions of G alpha(z) or the PTX-resistant mutants of G alpha(i2) and G alpha(oA). Moreover, G alpha(i2) was co-immunoprecipitated with the TrkA receptor from PC12 cell lysates. To discern the participation of various signaling intermediates, PC12 cells were treated with a panel of specific inhibitors prior to the NGF challenge. NGF-induced p38 MAPK phosphorylation was abolished by inhibitors of Src (PP1, PP2, and SU6656) and MEK1/2 (U0126). Inhibition of the p38 MAPK pathway also suppressed NGF-induced PC12 cell differentiation. In contrast, inhibitors of JAK2, phospholipase C, protein kinase C and Ca2+/calmodulin-dependent kinase II did not affect the ability of NGF to activate p38 MAPK. Collectively, these studies indicate that NGF-dependent p38 MAPK activity may be mediated via G(i2) protein, Src, and the MEK/ERK cascade. (c) 2008 Elsevier Inc. All rights reserved.
ISSN 0898-6568
Rights Cellular signalling © copyright 2008 Elsevier. The Journal's web site is located at
Language English
Format Article
Access View full-text via DOI
View full-text via Web of Science
View full-text via Scopus
Files in this item:
File Description Size Format
NGFGi2zsignalingCellularSign1.pdf 190144 B Adobe PDF
NGFp38FigsCelllularSign.ppt 13249024 B Microsoft Powerpoint