CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization

• DOI: 10.1194/jlr.m055004
• Publication Date: 2014-11-25T03:26:29Z
• Authors: Anita Sahu-Osen; Gabriela Montero-...; Matthias Schittmayer; Katarina Fritz; Anna Dinh; Yu-Fang Chang; Derek McMahon; Andras Boeszoermenyi; Irina Cornaciu; Deanna Russell; Monika Oberer; George M. Carman; Ruth Birner-Gruen...; Dawn L. Brasaemle
• Keywords: Perilipin; Adipose triglyceride lipase; Lipid droplet; Hormone-sensitive lipase

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), is phosphorylated and rapidly disperses into the cytoplasm, enabling coactivation. Because amino acid sequence murine has a predicted PKA consensus RKYS(239)S(240), we hypothesized that phosphorylation involved in this process. We show Ser239 substrate for using phosphoamino analysis, MS, immuno-blotting approaches study recombinant endogenous tissue. Phosphorylation neither increased nor impaired coactivation ATGL vitro. Moreover, was not required function increase triacylglycerol turnover human neutral storage disorder fibroblasts lack CGI-58. Both S239A/S240A-mutated localized 1A-coated cells. When activated, WT dispersed whereas substantial remained droplets. Perilipin also contributed dispersion. PKA-mediated dispersion from droplets, thereby increasing availability