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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.
- Source :
-
Journal of Biological Chemistry . 1/12/2007, Vol. 282 Issue 2, p996-1002. 7p. 1 Black and White Photograph, 1 Chart, 4 Graphs. - Publication Year :
- 2007
-
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 (fonskolin)-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 Pen 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 Pen A regulates ATGL-dependent lipolysis and identify serine 517 as the Pen A PKA site essential for this regulation. The contributions of other PKA sites to PKA-stimulated lipolysis are manifested only in the presence of phosphonylated or phosphomimetic serine 517. [ABSTRACT FROM AUTHOR]
- Subjects :
- *FAT cells
*LIPOLYSIS
*LIPASES
*PHOSPHORYLATION
*PROTEIN kinases
*GENETIC mutation
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 282
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23802001
- Full Text :
- https://doi.org/10.1074/jbc.M605770200