Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2
Authors
Yu, JianxiuDeng, Rong
Zhu, Helen H.
Zhang, Sharon S.
Zhu, Changhong
Montminy, Marc
Davis, Roger J.
Feng, Gen-Sheng
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2013-02-08Keywords
3T3 CellsAnimals
Fatty Acid Synthase, Type I
HeLa Cells
Humans
Lipid Metabolism
Liver
Mice
Mice, Knockout
Nuclear Proteins
Pancreas
Protein Tyrosine Phosphatase, Non-Receptor Type 11
*Proteolysis
Ubiquitin-Protein Ligases
p38 Mitogen-Activated Protein Kinases
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
Metadata
Show full item recordAbstract
The Src-homology 2 (SH2) domain-containing tyrosine phosphatase Shp2 has been known to regulate various signaling pathways triggered by receptor and cytoplasmic tyrosine kinases. Here we describe a novel function of Shp2 in control of lipid metabolism by mediating degradation of fatty acid synthase (FASN). p38-phosphorylated COP1 accumulates in the cytoplasm and subsequently binds FASN through Shp2 here as an adapter, leading to FASN-Shp2-COP1 complex formation and FASN degradation mediated by ubiquitination pathway. By fasting p38 is activated and stimulates FASN protein degradation in mice. Consistently, the FASN protein levels are dramatically elevated in mouse liver and pancreas in which Shp2/Ptpn11 is selectively deleted. Thus, this study identifies a new activity for Shp2 in lipid metabolism.Source
J Biol Chem. 2013 Feb 8;288(6):3823-30. doi: 10.1074/jbc.M112.397885. Epub 2012 Dec 26. Link to article on publisher's siteDOI
10.1074/jbc.M112.397885Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28322PubMed ID
23269672Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M112.397885