Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes

Miyoshi, Hideaki; Perfield, James W.; Souza, Sandra C.; Shen, Wen-Jun; Zhang, Hui-Hong; Stancheva, Zlatina S.; Kraemer, Fredric B.; Obin, Martin S.; Greenberg, Andrew S.

Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes

Miyoshi, Hideaki; Perfield, James W.; Souza, Sandra C. et al.

Journal of Biological Chemistry, 2007, 282(2), 996-1002

Permalink : https://hdl.handle.net/2115/17259

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アクセス権	open access
URI	https://hdl.handle.net/2115/17259
タイトル	Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes
著者	Miyoshi, Hideaki ; Perfield, James W. ; Souza, Sandra C. ; Shen, Wen-Jun ; Zhang, Hui-Hong ; Stancheva, Zlatina S. ; Kraemer, Fredric B. ; Obin, Martin S. ; Greenberg, Andrew S.
著者名 Miyoshi, Hideaki
著者名 Perfield, James W.
著者名 Souza, Sandra C.
著者名 Shen, Wen-Jun
著者名 Zhang, Hui-Hong
著者名 Stancheva, Zlatina S.
著者名 Kraemer, Fredric B.
著者名 Obin, Martin S.
著者名 Greenberg, Andrew S.
言語	英語
発行日	2007-01-12
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	282(2)
ページ	996-1002
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Copyright © 2007 by the American Society for Biochemistry and Molecular Biology
PISSN	0021-9258
EISSN	1083-351X
関連情報	PMID 17114792
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1074/jbc.M605770200