Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBPβ is required for hepatocyte proliferation induced by TGFα

被引：155
作者：
Buck, M
Poli, V
van der Geer, P
Chojkier, M
Hunter, T
机构：
[1] Salk Inst Biol Studies, La Jolla, CA 92037 USA
[2] Univ Dundee, Dept Biochem, Dundee DD1 4HN, Scotland
[3] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92037 USA
[4] Univ Calif San Diego, VA Med Ctr, Dept Med, La Jolla, CA 92037 USA
[5] Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92037 USA
来源：
MOLECULAR CELL | 1999年 / 4卷 / 06期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1016/S1097-2765(00)80237-3
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：
We report that TGF alpha induces activation of the p90 ribosomal S kinase (RSK), which results in the phosphorylation of rat C/EBP beta on Ser-105 and of mouse C/EBP beta on Thr-217 and concomitantly stimulates proliferation in differentiated hepatocytes. Moreover, C/EBP beta(-/-) mouse hepatocytes respond to TGF alpha when wild-type C/EBP beta is reexpressed, whereas they remain refractory to the growth effect of TGF alpha when expressing phosphoacceptor mutants rat C/EBP beta Ala-105 or mouse C/EBP beta Ala-217. In contrast, C/EBP beta(-/-) hepatocytes expressing the phosphorylation mimic mutants, rat C/EBP beta Asp-105 or mouse C/EBP beta Glu-217, exhibited marked proliferation in the absence of TGF alpha. Thus, a site-specific phosphorylation of the transcription factor C/EBP beta is critical for hepatocyte proliferation induced by TGF alpha and other stimuli that activate RSK.
引用
收藏
页码：1087 / 1092
页数：6
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