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
相关论文
共 24 条
[1]   A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY [J].
AKIRA, S ;
ISSHIKI, H ;
SUGITA, T ;
TANABE, O ;
KINOSHITA, S ;
NISHIO, Y ;
NAKAJIMA, T ;
HIRANO, T ;
KISHIMOTO, T .
EMBO JOURNAL, 1990, 9 (06) :1897-1906
[2]   STIMULATION OF COLLAGEN ALPHA(1)(I) GENE-EXPRESSION IS ASSOCIATED WITH LIPID-PEROXIDATION IN HEPATOCELLULAR INJURY - A LINK TO TISSUE FIBROSIS [J].
BEDOSSA, P ;
HOUGLUM, K ;
TRAUTWEIN, C ;
HOLSTEGE, A ;
CHOJKIER, M .
HEPATOLOGY, 1994, 19 (05) :1262-1271
[3]  
BOYLE WJ, 1991, METHOD ENZYMOL, V201, P110
[4]   LAP (NF-IL-6), A TISSUE-SPECIFIC TRANSCRIPTIONAL ACTIVATOR, IS AN INHIBITOR OF HEPATOMA-CELL PROLIFERATION [J].
BUCK, M ;
TURLER, H ;
CHOJKIER, M .
EMBO JOURNAL, 1994, 13 (04) :851-860
[5]   REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].
CAO, ZD ;
UMEK, RM ;
MCKNIGHT, SL .
GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552
[6]   PHOSPHORYLATION OF THE C-FOS TRANSREPRESSION DOMAIN BY MITOGEN-ACTIVATED PROTEIN-KINASE AND 90-KDA RIBOSOMAL S6 KINASE [J].
CHEN, RH ;
ABATE, C ;
BLENIS, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :10952-10956
[7]   REGULATION OF PP90RSK PHOSPHORYLATION AND S6 PHOSPHOTRANSFERASE ACTIVITY IN SWISS 3T3 CELLS BY GROWTH FACTOR-MEDIATED, PHORBOL ESTER-MEDIATED, AND CYCLIC AMP-MEDIATED SIGNAL TRANSDUCTION [J].
CHEN, RH ;
CHUNG, JK ;
BLENIS, J .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (04) :1861-1867
[8]   LAP, A NOVEL MEMBER OF THE C/EBP GENE FAMILY, ENCODES A LIVER-ENRICHED TRANSCRIPTIONAL ACTIVATOR PROTEIN [J].
DESCOMBES, P ;
CHOJKIER, M ;
LICHTSTEINER, S ;
FALVEY, E ;
SCHIBLER, U .
GENES & DEVELOPMENT, 1990, 4 (09) :1541-1551
[9]   CCAAT enhancer-binding protein β is required for normal hepatocyte proliferation in mice after partial hepatectomy [J].
Greenbaum, LE ;
Li, W ;
Cressman, DE ;
Peng, Y ;
Ciliberto, G ;
Poli, V ;
Taub, R .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (05) :996-1007
[10]   TGF-ALPHA OVEREXPRESSION IN TRANSGENIC MICE INDUCES LIVER NEOPLASIA AND ABNORMAL-DEVELOPMENT OF THE MAMMARY-GLAND AND PANCREAS [J].
JHAPPAN, C ;
STAHLE, C ;
HARKINS, RN ;
FAUSTO, N ;
SMITH, GH ;
MERLINO, GT .
CELL, 1990, 61 (06) :1137-1146
123