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Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation

Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptoch...

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Autores principales: Chaudhari, Amol, Gupta, Richa, Patel, Sonal, Velingkaar, Nikkhil, Kondratov, Roman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349790/
https://www.ncbi.nlm.nih.gov/pubmed/28100634
http://dx.doi.org/10.1091/mbc.E16-08-0624
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author Chaudhari, Amol
Gupta, Richa
Patel, Sonal
Velingkaar, Nikkhil
Kondratov, Roman
author_facet Chaudhari, Amol
Gupta, Richa
Patel, Sonal
Velingkaar, Nikkhil
Kondratov, Roman
author_sort Chaudhari, Amol
collection PubMed
description Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptochromes (CRYs)—transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry-deficient mice, and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling. In agreement, Cry-deficient mice have reduced body (∼30% reduction) and organ size. Down-regulation of IGF-1 upon Cry deficiency correlates with reduced Igf-1 mRNA expression in the liver and skeletal muscles. Igf-1 transcription is regulated through growth hormone–induced, JAK2 kinase–mediated phosphorylation of transcriptional factor STAT5B. The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the liver and skeletal muscles of Cry-deficient mice. At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which places CRY activity downstream from JAK2. Thus CRYs link the circadian clock and JAK-STAT signaling through control of STAT5B phosphorylation, which provides the mechanism for circadian rhythms in IGF signaling in vivo.
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spelling pubmed-53497902017-05-30 Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation Chaudhari, Amol Gupta, Richa Patel, Sonal Velingkaar, Nikkhil Kondratov, Roman Mol Biol Cell Articles Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptochromes (CRYs)—transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry-deficient mice, and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling. In agreement, Cry-deficient mice have reduced body (∼30% reduction) and organ size. Down-regulation of IGF-1 upon Cry deficiency correlates with reduced Igf-1 mRNA expression in the liver and skeletal muscles. Igf-1 transcription is regulated through growth hormone–induced, JAK2 kinase–mediated phosphorylation of transcriptional factor STAT5B. The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the liver and skeletal muscles of Cry-deficient mice. At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which places CRY activity downstream from JAK2. Thus CRYs link the circadian clock and JAK-STAT signaling through control of STAT5B phosphorylation, which provides the mechanism for circadian rhythms in IGF signaling in vivo. The American Society for Cell Biology 2017-03-15 /pmc/articles/PMC5349790/ /pubmed/28100634 http://dx.doi.org/10.1091/mbc.E16-08-0624 Text en © 2017 Chaudhari et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Chaudhari, Amol
Gupta, Richa
Patel, Sonal
Velingkaar, Nikkhil
Kondratov, Roman
Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title_full Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title_fullStr Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title_full_unstemmed Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title_short Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
title_sort cryptochromes regulate igf-1 production and signaling through control of jak2-dependent stat5b phosphorylation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349790/
https://www.ncbi.nlm.nih.gov/pubmed/28100634
http://dx.doi.org/10.1091/mbc.E16-08-0624
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