Role of STAT3 and PI 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons

Alonzi, Tonino, Middleton, Gayle, Wyatt, Sean Lee ORCID: https://orcid.org/0000-0002-0572-234X, Buchman, Vladimir L. ORCID: https://orcid.org/0000-0002-7631-8352, Ulrich, A. K. Betz, Muller, Werner, Musiani, Piero, Poli, Valeria and Davies, Alun M. ORCID: https://orcid.org/0000-0001-5841-8176 2001. Role of STAT3 and PI 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons. Molecular and Cellular Neuroscience 18 (3) , pp. 270-282. 10.1006/mcne.2001.1018

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Abstract

The binding of cytokines to the gp130 receptor activates the STAT3, MEK/MAPK, and PI3K/Akt signalling pathways. To assess the relative importance of these pathways in promoting the survival of cytokine-dependent neurons, we conditionally inactivated STAT3 in mice and inhibited MEK, PI3K, and Akt in cultured neurons using pharmacological reagents and by expressing specific inhibitory proteins. Inactivation of STAT3 enhanced the death of the cytokine-dependent sensory neurons of the nodoseganglion in vivo and substantially reduced the response of these neurons to CNTF and LIF in vitro. LY294002, an inhibitor of PI3K, but not PD98059, an inhibitor of MEK, markedly reduced the response of these neurons to CNTF, as did dominant-negative PI3K, dominant-negative Akt, and overexpression of Rukl (a natural PI3K inhibitor). These results demonstrate that STAT3 and PI3K/Akt signalling play major roles in mediating the survival response of neurons to cytokines

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history Q Science > QH Natural history > QH426 Genetics
Publisher:	Elsevier
ISSN:	1044-7431
Last Modified:	27 Oct 2022 08:25
URI:	https://orca.cardiff.ac.uk/id/eprint/62274

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