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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sahu-Osen, A; Montero-Moran, G; Schittmayer, M; Fritz, K; Dinh, A; Chang, YF; McMahon, D; Boeszoermenyi, A; Cornaciu, I; Russell, D; Oberer, M; Carman, GM; Birner-Gruenberger, R; Brasaemle, DL.
CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization.
J Lipid Res. 2015; 56(1):109-121
Doi: 10.1194/jlr.M055004
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- Führende Autor*innen der Med Uni Graz
- Birner-Grünberger Ruth
- Sahu-Osen Anita
- Co-Autor*innen der Med Uni Graz
- Fritz Katarina
- Schittmayer-Schantl Matthias
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- Abstract:
- 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 immuno-blotting 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. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- 1-Acylglycerol-3-Phosphate O-Acyltransferase - chemistry
- 1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism
- Adipocytes - cytology
- Adipocytes - drug effects
- Adipocytes - metabolism
- Amino Acid Sequence -
- Animals -
- COS Cells -
- Carrier Proteins - metabolism
- Cercopithecus aethiops -
- Colforsin - pharmacology
- Cyclic AMP-Dependent Protein Kinases - metabolism
- Gene Expression Regulation - drug effects
- Humans -
- Intracellular Space - drug effects
- Intracellular Space - metabolism
- Lipase - metabolism
- Male -
- Mice -
- Molecular Sequence Data -
- Perilipin-1 -
- Phosphoproteins - metabolism
- Phosphorylation - drug effects
- Protein Binding - drug effects
- Protein Transport - drug effects
- Recombinant Proteins - chemistry
- Recombinant Proteins - metabolism
- Serine - metabolism
- Find related publications in this database (Keywords)
- adipocytes
- adipose tissue
- adipose triglyceride lipase
- Chanarin Dorfman syndrome
- lipase
- lipid droplets
- lipolysis
- perilipin