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Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes

Su, CL; Sztalryd, C; Contreras, Juan Antonio LU ; Holm, Cecilia LU ; Kimmel, AR and Londos, C (2003) In Journal of Biological Chemistry 278(44). p.43615-43619
Abstract
Lipolysis in adipocytes governs the release of fatty acids for the supply of energy to various tissues of the body. This reaction is mediated by hormone-sensitive lipase (HSL), a cytosolic enzyme, and perilipin, which coats the lipid droplet surface in adipocytes. Both HSL and perilipin are substrates for polyphosphorylation by protein kinase A (PKA), and phosphorylation of perilipin is required to induce HSL to translocate from the cytosol to the surface of the lipid droplet, a critical step in the lipolytic reaction (Sztalryd C., Xu, G., Dorward, H., Tansey, J.T., Contreras, J.A, Kimmel, A. R., and Londos, C. (2003) J. Cell Biol. 161, 1093-1103). In the present paper we demonstrate that phosphorylation at one of the two more recently... (More)
Lipolysis in adipocytes governs the release of fatty acids for the supply of energy to various tissues of the body. This reaction is mediated by hormone-sensitive lipase (HSL), a cytosolic enzyme, and perilipin, which coats the lipid droplet surface in adipocytes. Both HSL and perilipin are substrates for polyphosphorylation by protein kinase A (PKA), and phosphorylation of perilipin is required to induce HSL to translocate from the cytosol to the surface of the lipid droplet, a critical step in the lipolytic reaction (Sztalryd C., Xu, G., Dorward, H., Tansey, J.T., Contreras, J.A, Kimmel, A. R., and Londos, C. (2003) J. Cell Biol. 161, 1093-1103). In the present paper we demonstrate that phosphorylation at one of the two more recently discovered PKA sites within HSL, serines 659 and 660, is also required to effect the translocation reaction. Translocation does not occur when these serines residues are mutated simultaneously to alanines. Also, mutation of the catalytic Ser-423 eliminates HSL translocation, showing that the inactive enzyme does not migrate to the lipid droplet upon PKA activation. Thus, HSL translocation requires the phosphorylation of both HSL and perilipin. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
278
issue
44
pages
43615 - 43619
publisher
ASBMB
external identifiers
  • wos:000186157000109
  • scopus:0242290249
ISSN
1083-351X
DOI
10.1074/jbc.M301809200
language
English
LU publication?
yes
id
39e41bf3-564a-4f71-9391-75998a70d498 (old id 297917)
date added to LUP
2007-09-22 13:25:41
date last changed
2018-02-18 03:39:20
@article{39e41bf3-564a-4f71-9391-75998a70d498,
  abstract     = {Lipolysis in adipocytes governs the release of fatty acids for the supply of energy to various tissues of the body. This reaction is mediated by hormone-sensitive lipase (HSL), a cytosolic enzyme, and perilipin, which coats the lipid droplet surface in adipocytes. Both HSL and perilipin are substrates for polyphosphorylation by protein kinase A (PKA), and phosphorylation of perilipin is required to induce HSL to translocate from the cytosol to the surface of the lipid droplet, a critical step in the lipolytic reaction (Sztalryd C., Xu, G., Dorward, H., Tansey, J.T., Contreras, J.A, Kimmel, A. R., and Londos, C. (2003) J. Cell Biol. 161, 1093-1103). In the present paper we demonstrate that phosphorylation at one of the two more recently discovered PKA sites within HSL, serines 659 and 660, is also required to effect the translocation reaction. Translocation does not occur when these serines residues are mutated simultaneously to alanines. Also, mutation of the catalytic Ser-423 eliminates HSL translocation, showing that the inactive enzyme does not migrate to the lipid droplet upon PKA activation. Thus, HSL translocation requires the phosphorylation of both HSL and perilipin.},
  author       = {Su, CL and Sztalryd, C and Contreras, Juan Antonio and Holm, Cecilia and Kimmel, AR and Londos, C},
  issn         = {1083-351X},
  language     = {eng},
  number       = {44},
  pages        = {43615--43619},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes},
  url          = {http://dx.doi.org/10.1074/jbc.M301809200},
  volume       = {278},
  year         = {2003},
}