The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects

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Abstract

The growth hormone receptor (GHR), although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK–STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling.

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Author and article information

Contributors

Farhad Dehkhoda: URI : http://frontiersin.org/people/u/467119

Christine M. M. Lee: URI : http://frontiersin.org/people/u/466883

Johan Medina: URI : http://frontiersin.org/people/u/467145

Andrew J. Brooks: URI : http://frontiersin.org/people/u/353029

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 13 February 2018

Publication date Collection: 2018

Volume: 9

Electronic Location Identifier: 35

Affiliations

[1] ¹The University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland , Brisbane, QLD, Australia

Author notes

Edited by: Stefan N. Constantinescu, Ludwig Cancer Research, Belgium

Reviewed by: Sandra Pellegrini, Institut Pasteur, France; Lily Huang, University of Texas Southwestern Medical Center, United States

*Correspondence: Andrew J. Brooks, a.brooks@ 123456uq.edu.au

Specialty section: This article was submitted to Molecular and Structural Endocrinology, a section of the journal Frontiers in Endocrinology

Article

DOI: 10.3389/fendo.2018.00035

PMC ID: 5816795

PubMed ID: 29487568

SO-VID: 1c987cf2-8e4e-4cad-bfde-89e306dadfba

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 24 July 2017

Date accepted : 29 January 2018

Page count

Figures: 6, Tables: 3, Equations: 0, References: 324, Pages: 23, Words: 20312

Funding

Funded by: National Health and Medical Research Council 10.13039/501100000925

Award ID: APP1084797

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