Article
- The EMBO Journal (2006) 25, 2377 - 2387
- doi:10.1038/sj.emboj.7601118
Published online: 4 May 2006
Subject Categories:
A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic 
-cells
Ke Ning1, Lisa C Miller1, Hilary A Laidlaw1, Laura A Burgess1, Nevin M Perera2, C Peter Downes2, Nick R Leslie2 and Michael LJ Ashford1
- Neurosciences Institute, Division of Pathology & Neuroscience, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK
- Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, UK
Correspondence to:
Michael LJ Ashford, Neurosciences Institute, Division of Pathology & Neuroscience, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK. Tel.: +44 1382 632497; Fax: +44 1382 667120; E-mail: m.l.j.ashford@dundee.ac.uk
Received 28 October 2005; Accepted 5 April 2006
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 in 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 
-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 PTEN in leptin signalling and indicate a mechanism by which leptin and insulin can produce PI3K dependent differential cellular outputs.
Keywords:
- insulin,
- leptin,
- phosphatase,
- PI3-kinase,
- PTEN
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