Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/6248

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

Authors Yung, Lisa Y.
Tso, Prudence H.
Wu, Eddy H. T.
Yu, Jowie C. H.
Ip, Nancy Y.
Wong, Yung H.
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.
Subjects
ERK
Src
ISSN 0898-6568
Rights Cellular signalling © copyright 2008 Elsevier. The Journal's web site is located at http://www.sciencedirect.com/
Language English
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