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Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes
Title: | Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes |
Authors: | Miyoshi, Hideaki Browse this author | Perfield, James W. Browse this author | Souza, Sandra C. Browse this author | Shen, Wen-Jun Browse this author | Zhang, Hui-Hong Browse this author | Stancheva, Zlatina S. Browse this author | Kraemer, Fredric B. Browse this author | Obin, Martin S. Browse this author | Greenberg, Andrew S. Browse this author |
Issue Date: | 12-Jan-2007 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Journal Title: | Journal of Biological Chemistry |
Volume: | 282 |
Issue: | 2 |
Start Page: | 996 |
End Page: | 1002 |
Publisher DOI: | 10.1074/jbc.M605770200 |
PMID: | 17114792 |
Abstract: | Phosphorylation of the lipid droplet-associated protein perilipin A (Peri A) mediates the actions of cyclic AMP-dependent protein kinase A (PKA) to stimulate triglyceride hydrolysis (lipolysis) in adipocytes. Studies addressing how Peri A PKA sites regulate adipocyte lipolysis have relied on non-adipocyte cell models, which express neither adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triglyceride catabolism in mice, nor the "downstream" lipase, hormone-sensitive lipase (HSL). ATGL and HSL are robustly expressed by adipocytes that we generated from murine embryonic fibroblasts of perilipin knock-out mice. Adenoviral expression of Peri A PKA site mutants in these cells reveals that mutation of serine 517 alone is sufficient to abrogate 95% of PKA (forskolin)-stimulated fatty acid (FA) and glycerol release. Moreover, a "phosphomimetic" (aspartic acid) substitution at serine 517 enhances PKA-stimulated FA release over levels obtained with wild type Peri A. Studies with ATGL-and HSL-directed small hairpin RNAs demonstrate that 1) ATGL activity is required for all PKA-stimulated FA and glycerol release in murine embryonic fibroblast adipocytes and 2) all PKA-stimulated FA release in the absence of HSL activity requires serine 517 phosphorylation. These results provide the first demonstration that Peri A regulates ATGL-dependent lipolysis and identify serine 517 as the Peri A PKA site essential for this regulation. The contributions of other PKA sites to PKA-stimulated lipolysis are manifested only in the presence of phosphorylated or phosphomimetic serine 517. Thus, serine 517 is a novel "master regulator" of PKA-stimulated adipocyte lipolysis. |
Rights: | Copyright © 2007 by the American Society for Biochemistry and Molecular Biology |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/17259 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 三好 秀明
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