Phosphorylation of the liver X receptors

Mingyi Chen; Michelle N. Bradley; Simon W. Beaven; Peter Tontonoz

doi:10.1016/j.febslet.2006.07.074

Phosphorylation of the liver X receptors

Mingyi Chen, Michelle N. Bradley, Simon W. Beaven, Peter Tontonoz

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, and inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis and metabolic labeling indicate LXRα is phosphorylated on serine 198 in the hinge region. This is a consensus target for the MAPK family. A phosphorylation-deficient mutant, LXRα S198A, remains nuclear and responds to ligands like the wild-type protein. The biological significance of LXR phosphorylation remains to be elucidated but could provide a novel mechanism for the regulation of LXR signaling pathways and cellular metabolism.

Original language	English (US)
Pages (from-to)	4835-4841
Number of pages	7
Journal	FEBS Letters
Volume	580
Issue number	20
DOIs	https://doi.org/10.1016/j.febslet.2006.07.074
State	Published - Sep 4 2006

Keywords

Cholesterol metabolism
Liver X receptor
Phosphorylation

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2006.07.074

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title = "Phosphorylation of the liver X receptors",

abstract = "The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, and inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis and metabolic labeling indicate LXRα is phosphorylated on serine 198 in the hinge region. This is a consensus target for the MAPK family. A phosphorylation-deficient mutant, LXRα S198A, remains nuclear and responds to ligands like the wild-type protein. The biological significance of LXR phosphorylation remains to be elucidated but could provide a novel mechanism for the regulation of LXR signaling pathways and cellular metabolism.",

keywords = "Cholesterol metabolism, Liver X receptor, Phosphorylation",

author = "Mingyi Chen and Bradley, {Michelle N.} and Beaven, {Simon W.} and Peter Tontonoz",

note = "Funding Information: This work was supported by postdoctoral fellowship from the American Heart Association (M.C.), NIH Training Grant #T32-DK07180-30 (S.B.) and the Specialty Training and Advanced Research (STAR) Program at UCLA (S.B.) and Grants from the NIH (HL66088 and HL30568). P.T. is an Investigator with the Howard Hughes Medical Institute at UCLA. We thank Timothy M. Willson (GlaxoSmithKline) for T0901317 and Jae Bum Kim (Seoul National Unviersity, Korea) for the generous gift of LXRα antibodies.",

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doi = "10.1016/j.febslet.2006.07.074",

language = "English (US)",

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T1 - Phosphorylation of the liver X receptors

AU - Chen, Mingyi

AU - Bradley, Michelle N.

AU - Beaven, Simon W.

AU - Tontonoz, Peter

N1 - Funding Information: This work was supported by postdoctoral fellowship from the American Heart Association (M.C.), NIH Training Grant #T32-DK07180-30 (S.B.) and the Specialty Training and Advanced Research (STAR) Program at UCLA (S.B.) and Grants from the NIH (HL66088 and HL30568). P.T. is an Investigator with the Howard Hughes Medical Institute at UCLA. We thank Timothy M. Willson (GlaxoSmithKline) for T0901317 and Jae Bum Kim (Seoul National Unviersity, Korea) for the generous gift of LXRα antibodies.

PY - 2006/9/4

Y1 - 2006/9/4

N2 - The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, and inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis and metabolic labeling indicate LXRα is phosphorylated on serine 198 in the hinge region. This is a consensus target for the MAPK family. A phosphorylation-deficient mutant, LXRα S198A, remains nuclear and responds to ligands like the wild-type protein. The biological significance of LXR phosphorylation remains to be elucidated but could provide a novel mechanism for the regulation of LXR signaling pathways and cellular metabolism.

AB - The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, and inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis and metabolic labeling indicate LXRα is phosphorylated on serine 198 in the hinge region. This is a consensus target for the MAPK family. A phosphorylation-deficient mutant, LXRα S198A, remains nuclear and responds to ligands like the wild-type protein. The biological significance of LXR phosphorylation remains to be elucidated but could provide a novel mechanism for the regulation of LXR signaling pathways and cellular metabolism.

KW - Cholesterol metabolism

KW - Liver X receptor

KW - Phosphorylation

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JO - FEBS Letters

JF - FEBS Letters

IS - 20

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Phosphorylation of the liver X receptors

Abstract

Keywords

ASJC Scopus subject areas

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