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CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization
CGI-58/ABHD5 coactivates adipose triglyceride lipase (ATGL). In adipocytes, CGI-58 binds to perilipin 1A on lipid droplets under basal conditions, preventing interaction with ATGL. Upon activation of protein kinase A (PKA), perilipin 1A is phosphorylated and CGI-58 rapidly disperses into the cytopla...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274058/ https://www.ncbi.nlm.nih.gov/pubmed/25421061 http://dx.doi.org/10.1194/jlr.M055004 |
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author | Sahu-Osen, Anita Montero-Moran, Gabriela Schittmayer, Matthias Fritz, Katarina Dinh, Anna Chang, Yu-Fang McMahon, Derek Boeszoermenyi, Andras Cornaciu, Irina Russell, Deanna Oberer, Monika Carman, George M. Birner-Gruenberger, Ruth Brasaemle, Dawn L. |
author_facet | Sahu-Osen, Anita Montero-Moran, Gabriela Schittmayer, Matthias Fritz, Katarina Dinh, Anna Chang, Yu-Fang McMahon, Derek Boeszoermenyi, Andras Cornaciu, Irina Russell, Deanna Oberer, Monika Carman, George M. Birner-Gruenberger, Ruth Brasaemle, Dawn L. |
author_sort | Sahu-Osen, Anita |
collection | PubMed |
description | CGI-58/ABHD5 coactivates adipose triglyceride lipase (ATGL). In adipocytes, CGI-58 binds to perilipin 1A on lipid droplets under basal conditions, preventing interaction with ATGL. Upon activation of protein kinase A (PKA), perilipin 1A is phosphorylated and CGI-58 rapidly disperses into the cytoplasm, enabling lipase coactivation. Because the amino acid sequence of murine CGI-58 has a predicted PKA consensus sequence of RKYS(239)S(240), we hypothesized that phosphorylation of CGI-58 is involved in this process. We show that Ser239 of murine CGI-58 is a substrate for PKA using phosphoamino acid analysis, MS, and immunoblotting approaches to study phosphorylation of recombinant CGI-58 and endogenous CGI-58 of adipose tissue. Phosphorylation of CGI-58 neither increased nor impaired coactivation of ATGL in vitro. Moreover, Ser239 was not required for CGI-58 function to increase triacylglycerol turnover in human neutral lipid storage disorder fibroblasts that lack endogenous CGI-58. Both CGI-58 and S239A/S240A-mutated CGI-58 localized to perilipin 1A-coated lipid droplets in cells. When PKA was activated, WT CGI-58 dispersed into the cytoplasm, whereas substantial S239A/S240A-mutated CGI-58 remained on lipid droplets. Perilipin phosphorylation also contributed to CGI-58 dispersion. PKA-mediated phosphorylation of CGI-58 is required for dispersion of CGI-58 from perilipin 1A-coated lipid droplets, thereby increasing CGI-58 availability for ATGL coactivation. |
format | Online Article Text |
id | pubmed-4274058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-42740582015-01-01 CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization Sahu-Osen, Anita Montero-Moran, Gabriela Schittmayer, Matthias Fritz, Katarina Dinh, Anna Chang, Yu-Fang McMahon, Derek Boeszoermenyi, Andras Cornaciu, Irina Russell, Deanna Oberer, Monika Carman, George M. Birner-Gruenberger, Ruth Brasaemle, Dawn L. J Lipid Res Research Articles CGI-58/ABHD5 coactivates adipose triglyceride lipase (ATGL). In adipocytes, CGI-58 binds to perilipin 1A on lipid droplets under basal conditions, preventing interaction with ATGL. Upon activation of protein kinase A (PKA), perilipin 1A is phosphorylated and CGI-58 rapidly disperses into the cytoplasm, enabling lipase coactivation. Because the amino acid sequence of murine CGI-58 has a predicted PKA consensus sequence of RKYS(239)S(240), we hypothesized that phosphorylation of CGI-58 is involved in this process. We show that Ser239 of murine CGI-58 is a substrate for PKA using phosphoamino acid analysis, MS, and immunoblotting approaches to study phosphorylation of recombinant CGI-58 and endogenous CGI-58 of adipose tissue. Phosphorylation of CGI-58 neither increased nor impaired coactivation of ATGL in vitro. Moreover, Ser239 was not required for CGI-58 function to increase triacylglycerol turnover in human neutral lipid storage disorder fibroblasts that lack endogenous CGI-58. Both CGI-58 and S239A/S240A-mutated CGI-58 localized to perilipin 1A-coated lipid droplets in cells. When PKA was activated, WT CGI-58 dispersed into the cytoplasm, whereas substantial S239A/S240A-mutated CGI-58 remained on lipid droplets. Perilipin phosphorylation also contributed to CGI-58 dispersion. PKA-mediated phosphorylation of CGI-58 is required for dispersion of CGI-58 from perilipin 1A-coated lipid droplets, thereby increasing CGI-58 availability for ATGL coactivation. The American Society for Biochemistry and Molecular Biology 2015-01 /pmc/articles/PMC4274058/ /pubmed/25421061 http://dx.doi.org/10.1194/jlr.M055004 Text en Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/3.0/ Author’s Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Research Articles Sahu-Osen, Anita Montero-Moran, Gabriela Schittmayer, Matthias Fritz, Katarina Dinh, Anna Chang, Yu-Fang McMahon, Derek Boeszoermenyi, Andras Cornaciu, Irina Russell, Deanna Oberer, Monika Carman, George M. Birner-Gruenberger, Ruth Brasaemle, Dawn L. CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title | CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title_full | CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title_fullStr | CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title_full_unstemmed | CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title_short | CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization |
title_sort | cgi-58/abhd5 is phosphorylated on ser239 by protein kinase a: control of subcellular localization |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274058/ https://www.ncbi.nlm.nih.gov/pubmed/25421061 http://dx.doi.org/10.1194/jlr.M055004 |
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