A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic β-cells

Ke Ning, Lisa C. Miller, Hilary A. Laidlaw, Laura A. Burgess, Nevin M. Perera, C. Peter Downes, Nick R. Leslie, Michael L. J. Ashford

    Research output: Contribution to journalArticle

    86 Citations (Scopus)

    Abstract

    In obesity and diabetes, the ability of hypothalamic neurons to sense and transduce changes in leptin and insulin levels is compromised. The effects of both hormones require intracellular signalling via the PI3-kinase pathway, which is inhibited by the phosphatase PTEN. We show that leptin-stimulated F-actin depolymerization mouse hypothalamic cells is inhibited by PTEN, a process involving independent effects of both its lipid and protein phosphatase activities. Potentially mediating this F-actin depolymerization, leptin, but not insulin, stimulated the phosphorylation of PTEN in a CK2 dependent manner, and inhibited its phosphatase activity. Similarly, hyperpolarization of mouse pancreatic ß-cells by leptin also requires coincident PtdIns(3,4,5)P3 generation and actin depolymerization, and could be inhibited by mechanisms requiring both the lipid and protein phosphatase activities of PTEN. These results demonstrate a critical role for PT in leptin signalling and indicate a mechanism by which leptin and insulin can produce PI3K dependent differentia cellular outputs.

    Original languageEnglish
    Pages (from-to)2377-2387
    Number of pages11
    JournalThe EMBO Journal
    Volume25
    Issue number11
    DOIs
    Publication statusPublished - Jun 2006

    Fingerprint

    Leptin
    Cells
    Cell Line
    Depolymerization
    PTEN Phosphohydrolase
    Actins
    Phosphoprotein Phosphatases
    Insulin
    Phosphatidylinositol 3-Kinases
    Lipids
    Phosphorylation
    Medical problems
    Phosphoric Monoester Hydrolases
    Neurons
    Obesity
    Hormones

    Keywords

    • Insulin
    • Leptin
    • Phosphatase
    • PI 3-kinase
    • PTEN

    Cite this

    Ning, Ke ; Miller, Lisa C. ; Laidlaw, Hilary A. ; Burgess, Laura A. ; Perera, Nevin M. ; Downes, C. Peter ; Leslie, Nick R. ; Ashford, Michael L. J. / A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic β-cells. In: The EMBO Journal. 2006 ; Vol. 25, No. 11. pp. 2377-2387.
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    abstract = "In obesity and diabetes, the ability of hypothalamic neurons to sense and transduce changes in leptin and insulin levels is compromised. The effects of both hormones require intracellular signalling via the PI3-kinase pathway, which is inhibited by the phosphatase PTEN. We show that leptin-stimulated F-actin depolymerization mouse hypothalamic cells is inhibited by PTEN, a process involving independent effects of both its lipid and protein phosphatase activities. Potentially mediating this F-actin depolymerization, leptin, but not insulin, stimulated the phosphorylation of PTEN in a CK2 dependent manner, and inhibited its phosphatase activity. Similarly, hyperpolarization of mouse pancreatic {\ss}-cells by leptin also requires coincident PtdIns(3,4,5)P3 generation and actin depolymerization, and could be inhibited by mechanisms requiring both the lipid and protein phosphatase activities of PTEN. These results demonstrate a critical role for PT in leptin signalling and indicate a mechanism by which leptin and insulin can produce PI3K dependent differentia cellular outputs.",
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    author = "Ke Ning and Miller, {Lisa C.} and Laidlaw, {Hilary A.} and Burgess, {Laura A.} and Perera, {Nevin M.} and Downes, {C. Peter} and Leslie, {Nick R.} and Ashford, {Michael L. J.}",
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    Ning, K, Miller, LC, Laidlaw, HA, Burgess, LA, Perera, NM, Downes, CP, Leslie, NR & Ashford, MLJ 2006, 'A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic β-cells', The EMBO Journal, vol. 25, no. 11, pp. 2377-2387. https://doi.org/10.1038/sj.emboj.7601118

    A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic β-cells. / Ning, Ke; Miller, Lisa C.; Laidlaw, Hilary A.; Burgess, Laura A.; Perera, Nevin M.; Downes, C. Peter; Leslie, Nick R.; Ashford, Michael L. J.

    In: The EMBO Journal, Vol. 25, No. 11, 06.2006, p. 2377-2387.

    Research output: Contribution to journalArticle

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    AU - Leslie, Nick R.

    AU - Ashford, Michael L. J.

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