Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B.

Owen, C and Lees, E K and Mody, N and Delibegović, M (2015) Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B. Diabetes & metabolism, 41 (1). pp. 95-101. ISSN 1878-1780

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Abstract

Protein tyrosine phosphatase 1B (PTP1B) regulates various signalling pathways including insulin, leptin, IGF-1 and growth hormone (GH) signalling. Transmission of the GH signal depends on Janus kinase 2 (JAK2), which is how PTP1B is thought to modulate GH signalling in the liver, based on studies utilising global PTP1B knockout mice (Ptp1b(-/-)). Here, we investigated the liver-specific role of PTP1B in GH signalling, using liver-specific Ptp1b(-/-) mice (alb-crePtp1b(-/-)), under physiological (chow) or insulin resistant (high-fat diet [HFD]) feeding conditions. Body weight and adiposity were comparable between female alb-crePtp1b(-/-) and Ptp1b(fl/fl) control mice. On chow diet, under 48-hour fasting GH-resistant conditions, GH stimulation in vivo led to a robust stimulation of the JAK-STAT signalling pathway. Alb-crePtp1b(-/-) mice exhibited significantly higher GH-induced JAK2 phosphorylation and SOCS3 gene expression post-GH stimulation. However, STAT3, STAT5 and ERK1/2 phosphorylation and SOCS2 gene expression were similar between groups. Interestingly, GH-induced mTOR phosphorylation was significantly higher in alb-crePtp1b(-/-) mice 5-min post-GH stimulation compared to controls, revealing this part of the pathway under direct control of PTP1B. Under ad lib HFD-fed conditions, GH-induced STAT5 phosphorylation significantly increased in alb-crePtp1b(-/-) mice only, with no alterations in the controls. Overall, our data demonstrate that liver-specific PTP1B deletion leads to significant alterations in GH signalling with increased JAK2, STAT5 and mTOR phosphorylation and SOCS3 gene expression.

Item Type: Article
Additional Information and Comments: “NOTICE: this is the author’s version of a work that was accepted for publication in Diabetes & Metabolism. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Diabetes and Metabolism, [VOL 41, ISSUE 1, (February 2015)] DOI#10.1016/j.diabet.2014.02.008¨
Faculty / Department: Faculty of Science > School of Health Sciences
Depositing User: Emma Lees
Date Deposited: 08 Apr 2016 08:41
Last Modified: 08 Apr 2016 08:41
URI: http://hira.hope.ac.uk/id/eprint/1032

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