| Title : CGI-58\/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization - Sahu-Osen_2015_J.Lipid.Res_56_109 |
| Author(s) : 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 |
| Ref : J Lipid Res , 56 :109 , 2015 |
| 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. |
| ESTHER : Sahu-Osen_2015_J.Lipid.Res_56_109 |
| PubMedSearch : Sahu-Osen_2015_J.Lipid.Res_56_109 |
| PubMedID: 25421061 |
| Gene_locus related to this paper: human-ABHD5 |
| Gene_locus related to this paper: human-ABHD5 |
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 (2015)
CGI-58\/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization
J Lipid Res
56 :109
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 (2015)
J Lipid Res
56 :109