ADD1/SREBP-1c mediates insulin-induced gene expression linked to the MAP kinase pathway

被引:71
作者
Kotzka, J [1 ]
Müller-Wieland, D [1 ]
Koponen, A [1 ]
Njamen, D [1 ]
Kremer, L [1 ]
Roth, G [1 ]
Munck, M [1 ]
Knebel, B [1 ]
Krone, W [1 ]
机构
[1] Univ Cologne, Klin & Poliklin Innere Med 2, Ctr Mol Med, Cologne, Germany
关键词
D O I
10.1006/bbrc.1998.9161
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this study was to define the role of sterol regulatory element binding protein (SREBP)-1c, the human homologue to ADD1 (adipocyte determination- and differentiation-dependent factor 1), in insulin-induced gene expression. Transfection studies using SREBP-1-deficient cells and a LDL receptor promoter fragment containing the ADD1/SREBP-1c binding side showed that the effects of insulin and PDGF were abolished compared to control cells and completely reconstituted by overexpressing ADD1/SREBP-1c. Overexpression of upstream activators of MAP kinases, like MEKK1 or MEK1, demonstrated that ADD1/SREBP-1c-mediated effects of insulin and PDGF might be linked to the MAP kinase cascade. The recombinant N-terminal domain of ADD1/SREBP-1c was phosphorylated predominantly on serine and slightly on threonine residues by MAP kinases ERK1 and ERK2 in vitro. This was reversible by alkaline phosphatase. We conclude that ADD1/SREBP-1c mediates gene regulatory effects of insulin as well as PDGF and that this signalling is linked to the MAP kinase cascade. (C) 1998 Academic Press.
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页码:375 / 379
页数:5
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