Insulin stimulates cAMP-response element binding protein activity in HepG2 and 3T3-L1 cell lines

被引:79
作者
Klemm, DJ
Roesler, WJ
Boras, T
Colton, LA
Felder, K
Reusch, JEB
机构
[1] Vet Affairs Med Ctr, Sect Endocrinol 111H, Res Serv, Denver, CO 80220 USA
[2] Natl Jewish Ctr Immunol & Resp Med, Dept Allergy & Clin Immunol, Denver, CO 80206 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80220 USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80220 USA
[5] Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada
关键词
D O I
10.1074/jbc.273.2.917
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
Earlier studies from our laboratory demonstrated an insulin-mediated increase in cAMP-response element binding protein (CREB) phosphorylation. In this report, we show that insulin stimulates both CREB phosphorylation and transcriptional activation in HepG2 and 3T3-L1 cell lines, models of insulin sensitive tissues. Insulin stimulated the phosphorylation of CREB at serine 133, the protein kinase A site, and mutation of serine 133 to alanine blocked the insulin effect. Many of the signaling pathways known to be activated by insulin have been implicated in CREB phosphorylation and activation, The ability of insulin to induce CREB phosphorylation and activity was efficiently blocked by PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK1), but not significantly by rapamycin or wortmannin. Likewise, expression of dominant negative forms of Raf-1 completely blocked insulin-stimulated CREB transcriptional activity. Finally, we demonstrate an essential role for CREB in insulin activation of fatty-acid synthase and fatty acid binding protein (FABP) indicating the potential tial physiologic relevance of insulin regulation of CREB. In summary, insulin regulates CREB transcriptional activity in insulin-sensitive tissues via the Raf --> MEK pathway and has an impact on physiologically relevant genes in these cells.
引用
收藏
页码:917 / 923
页数:7
相关论文
共 42 条
[1]   REGULATION OF THE CYTOSOLIC ASPARTATE-AMINOTRANSFERASE HOUSEKEEPING GENE PROMOTER BY GLUCOCORTICOIDS, CAMP, AND INSULIN [J].
AGGERBECK, M ;
GARLATTI, M ;
FEILLEUXDUCHE, S ;
VEYSSIER, C ;
DAHESHIA, M ;
HANOUNE, J ;
BAROUKI, R .
BIOCHEMISTRY, 1993, 32 (35) :9065-9072
[2]  
ARMSTRONG R, 1995, MOL CELL BIOL, V15, P1826
[3]   CIS-REGULATION OF THE L-TYPE PYRUVATE-KINASE GENE PROMOTER BY GLUCOSE, INSULIN AND CYCLIC-AMP [J].
BERGOT, MO ;
DIAZGUERRA, MJM ;
PUZENAT, N ;
RAYMONDJEAN, M ;
KAHN, A .
NUCLEIC ACIDS RESEARCH, 1992, 20 (08) :1871-1878
[4]  
BOKAR JA, 1988, J BIOL CHEM, V263, P19740
[5]  
CIFUENTES ME, 1991, J BIOL CHEM, V266, P1557
[6]  
DePaolo D, 1996, MOL CELL BIOL, V16, P1450
[7]  
ELMAGHRABI MR, 1991, J BIOL CHEM, V266, P2115
[8]   PHOSPHORYLATION OF CREB BY CAM-KINASE-IV ACTIVATED BY CAM-KINASE-IV KINASE [J].
ENSLEN, H ;
TOKUMITSU, H ;
SODERLING, TR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 207 (03) :1038-1043
[9]   REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-EXPRESSION BY INSULIN - USE OF THE STABLE TRANSFECTION APPROACH TO LOCATE AN INSULIN RESPONSIVE SEQUENCE [J].
FOREST, CD ;
OBRIEN, RM ;
LUCAS, PC ;
MAGNUSON, MA ;
GRANNER, DK .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (09) :1302-1310
[10]   NERVE GROWTH-FACTOR ACTIVATES A RAS-DEPENDENT PROTEIN-KINASE THAT STIMULATES C-FOS TRANSCRIPTION PHOSPHORYLATION OF CREB [J].
GINTY, DD ;
BONNI, A ;
GREENBERG, ME .
CELL, 1994, 77 (05) :713-725