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

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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.

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Acknowledgements

This work was supported in part by grants from the Research Grants Council of Hong Kong (HKUST 3/03C), the University Grants Committee (AoE/B-15/01), and the Hong Kong Jockey Club. NYI and YHW were recipients of the Croucher Senior Research Fellowship.

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  1. Department of Biochemistry, The Molecular Neuroscience Center, The Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Prudence H. Tso, Christina J. Morris, Lisa Y. Yung, Nancy Y. Ip & Yung H. Wong

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  1. Prudence H. Tso
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  2. Christina J. Morris
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Correspondence to Yung H. Wong.

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Tso, P.H., Morris, C.J., Yung, L.Y. et al. Multiple Gi Proteins Participate in Nerve Growth Factor-Induced Activation of c-Jun N-terminal Kinases in PC12 Cells. Neurochem Res 34, 1101–1112 (2009). https://doi.org/10.1007/s11064-008-9880-9

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