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

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

Bibliographic Details
Main Author: CHAUDHARI, AMOL SANTOSH
Language:English
Published: Cleveland State University / OhioLINK 2017
Subjects:
Molecular Biology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=csu1499875265771664
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-csu14998752657716642021-08-03T07:03:09Z Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation CHAUDHARI, AMOL SANTOSH Molecular Biology 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 CRY's 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. 2017-07-18 English text Cleveland State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=csu1499875265771664 http://rave.ohiolink.edu/etdc/view?acc_num=csu1499875265771664 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Molecular Biology
spellingShingle Molecular Biology
CHAUDHARI, AMOL SANTOSH
Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation
author CHAUDHARI, AMOL SANTOSH
author_facet CHAUDHARI, AMOL SANTOSH
author_sort CHAUDHARI, AMOL SANTOSH
title 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_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_sort cryptochromes regulate igf-1 production and signaling through control of jak2-dependent stat5b phosphorylation
publisher Cleveland State University / OhioLINK
publishDate 2017
url http://rave.ohiolink.edu/etdc/view?acc_num=csu1499875265771664
work_keys_str_mv AT chaudhariamolsantosh cryptochromesregulateigf1productionandsignalingthroughcontrolofjak2dependentstat5bphosphorylation
_version_ 1719452387922411520

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