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

T Alonzi, Gayle Helane Middleton, S Wyatt, V Buchman, U Betz, W Muller, P Musiani, V Poli, AM Davies

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)

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 an 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 nodose ganglion 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 Ruk(1) (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.

Original languageEnglish
Pages (from-to)270-282
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume18
Issue number3
DOIs
Publication statusPublished - Sept 2001

Keywords

  • NERVE GROWTH-FACTOR
  • KINASE-DEPENDENT PATHWAY
  • KAPPA-B ACTIVATION
  • BCL-X-L
  • SYMPATHETIC NEURONS
  • PROTEIN-KINASE
  • PHOSPHATIDYLINOSITOL 3-KINASE
  • CELL-DEATH
  • CNTF RECEPTOR
  • TRANSCRIPTION FACTOR

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