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

页码：1087 / 1092

页数：6

共 24 条

[11] NOVEL MECHANISM OF C/EBP-BETA (NF-M) TRANSCRIPTIONAL CONTROL - ACTIVATION THROUGH DEREPRESSION [J].