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PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart

The Rab GTPase activating protein (RabGAP), AS160/TBC1D4, is an important substrate of protein kinase B (PKB), and regulates insulin-stimulated trafficking of glucose transporter 4. Besides, AS160/TBC1D4 has also been shown to regulate trafficking of many other membrane proteins including FA translo...

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Autores principales: Quan, Chao, Xie, Bingxian, Wang, Hong Yu, Chen, Shuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414484/
https://www.ncbi.nlm.nih.gov/pubmed/25923736
http://dx.doi.org/10.1371/journal.pone.0124491
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author Quan, Chao
Xie, Bingxian
Wang, Hong Yu
Chen, Shuai
author_facet Quan, Chao
Xie, Bingxian
Wang, Hong Yu
Chen, Shuai
author_sort Quan, Chao
collection PubMed
description The Rab GTPase activating protein (RabGAP), AS160/TBC1D4, is an important substrate of protein kinase B (PKB), and regulates insulin-stimulated trafficking of glucose transporter 4. Besides, AS160/TBC1D4 has also been shown to regulate trafficking of many other membrane proteins including FA translocase/CD36 in cardiomyocytes. However, it is not clear whether it plays any role in regulating heart functions in vivo. Here, we found that PKB-mediated phosphorylation of Thr(649) on AS160/TBC1D4 represented one of the major PAS-binding signals in the heart in response to insulin. Mutation of Thr(649) to a non-phosphorylatable alanine increased the R-wave amplitude in the AS160(Thr649Ala) knockin mice. However, this knockin mutation did not affect the heart functions under both normal and infarct conditions. Interestingly, myocardial infarction induced the expression of a related RabGAP, TBC1D1, in the infarct zone as well as in the border zone. Together, these data show that the Thr(649) phosphorylation of AS160/TBC1D4 plays an important role in the heart’s electrical conduction system through regulating the R-wave amplitude.
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spelling pubmed-44144842015-05-07 PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart Quan, Chao Xie, Bingxian Wang, Hong Yu Chen, Shuai PLoS One Research Article The Rab GTPase activating protein (RabGAP), AS160/TBC1D4, is an important substrate of protein kinase B (PKB), and regulates insulin-stimulated trafficking of glucose transporter 4. Besides, AS160/TBC1D4 has also been shown to regulate trafficking of many other membrane proteins including FA translocase/CD36 in cardiomyocytes. However, it is not clear whether it plays any role in regulating heart functions in vivo. Here, we found that PKB-mediated phosphorylation of Thr(649) on AS160/TBC1D4 represented one of the major PAS-binding signals in the heart in response to insulin. Mutation of Thr(649) to a non-phosphorylatable alanine increased the R-wave amplitude in the AS160(Thr649Ala) knockin mice. However, this knockin mutation did not affect the heart functions under both normal and infarct conditions. Interestingly, myocardial infarction induced the expression of a related RabGAP, TBC1D1, in the infarct zone as well as in the border zone. Together, these data show that the Thr(649) phosphorylation of AS160/TBC1D4 plays an important role in the heart’s electrical conduction system through regulating the R-wave amplitude. Public Library of Science 2015-04-29 /pmc/articles/PMC4414484/ /pubmed/25923736 http://dx.doi.org/10.1371/journal.pone.0124491 Text en © 2015 Quan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Quan, Chao
Xie, Bingxian
Wang, Hong Yu
Chen, Shuai
PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title_full PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title_fullStr PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title_full_unstemmed PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title_short PKB-Mediated Thr(649) Phosphorylation of AS160/TBC1D4 Regulates the R-Wave Amplitude in the Heart
title_sort pkb-mediated thr(649) phosphorylation of as160/tbc1d4 regulates the r-wave amplitude in the heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414484/
https://www.ncbi.nlm.nih.gov/pubmed/25923736
http://dx.doi.org/10.1371/journal.pone.0124491
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