Hormone-sensitive lipase - New roles for an old enzyme

被引：185

作者：

Yeaman, Stephen J. ^{[1
]}

机构：

[1] Sch. of Cell and Molec. Biosciences, Medical School, University of Newcastle

来源：

Biochemical Journal | 2004年 / 379卷 / 01期

关键词：

β-cell; Cholesterol metabolism; Hormone-sensitive lipase; Lipolysis; Macrophage; Perilipin;

D O I：

10.1042/BJ20031811

中图分类号：

学科分类号：

摘要：

Although described initially as an intracellular adipocyte-specific triacylglycerol lipase, it is now clear that HSL (hormone-sensitive lipase) is expressed in multiple tissues and plays a number of roles in lipid metabolism, including that of a neutral cholesteryl ester hydrolase. The major isoform is a single polypeptide with a moleclar mass of approx. 84 kDa and which comprises three major domains: a catalytic domain, a regulatory domain encoding several phosphorylation sites and an N-terminal domain involved in protein-protein and protein-lipid interactions. The activity of HSL is regulated acutely by several mechanisms, including reversible phosphorylation by a number of different protein kinases, translocation to different sites within the cell and interaction with a number of proteins, some of which may serve to direct the inhibitory products of HSL away from the protein. It is also apparent from work with HSL null mice that more than one enzyme species may be classified as a hormone-sensitive lipase. The possible presence of HSL in macrophages remains controversial, and the role of the protein in pancreatic β-cells has yet to be fully elucidated. Altered expression of HSL in different cell types may be associated with a number of pathological states, including obesity, atherosclerosis and Type II diabetes.

引用

页码：11 / 22

页数：11

共 145 条

[41] Olsson H., Stralfors P., Belfrage P., Phosphorylation of the basal site of hormone-sensitive lipase by glycogen synthase kinase-4, FEBS Lett., 209, pp. 175-180, (1986)
[42] Anthonsen M.W., Ronnstrand L., Wernstedt C., Degerman E., Holm C., Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro, J. Biol. Chem., 273, pp. 215-221, (1998)
[43] Shen W.-J., Patel S., Natu V., Kraemer F.B., Mutational analysis of structural features of rat hormone-sensitive lipase, Biochemistry, 37, pp. 8973-8979, (1998)
[44] Vossier M.R., Yao H., York R.D., Pan M.-G., Rim C.S., Stork P.J.S., cAMP activates MAP kinase and Elk-1 through a B-Raf and Rap1-dependent pathway, Cell, 89, pp. 73-82, (1997)
[45] Wood S.L., Emmison N., Borthwick A.C., Yeaman S.J., The protein phosphatases responsible for dephosphorylation of hormone-sensitive lipase in isolated rat adipocytes, Biochem. J., 295, pp. 531-535, (1993)
[46] Londos C., Honnor R.C., Dhillon G.S., cAMP-dependent protein kinase and lipolysis in rat adipocytes. Multiple modes of insulin regulation of lipolysis and regulation of insulin responses by adenylate cyclase regulators, J. Biol. Chem., 260, pp. 15139-15145, (1985)
[47] Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K., Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M., Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt, Mol. Cell. Biol., 19, pp. 6286-6296, (1999)
[48] Stralfors P., Honnor R.C., Insulin-induced dephosphorylation of hormone-sensitive lipase. Correlation with lipolysis and cAMP-dependent protein kinase activity, Eur. J. Biochem., 182, pp. 379-385, (1989)
[49] Asada N., Takahashi Y., Wada M., Naito N., Uchida H., Ikeda M., Honjo M., GH induced lipolysis stimulation in 3T3-L1 adipocytes stably expressing hGHR: Analysis on signalling pathway and activity of 20K hGH, Mol. Cell. Endocrinol., 162, pp. 121-129, (2000)
[50] Sengenes C., Bouloumie A., Hauner H., Berlan M., Busse R., Lafontan M., Galitzky J., Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone sensitive lipase phosphorylation in human adipocytes, J. Biol. Chem., 278, pp. 48617-48626, (2003)

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