Novel pathway of insulin signaling involving Stat1alpha in Hep3B cells.
STAT proteins are important transcription factors that regulate cell growth and differentiation. To elucidate the molecular mechanisms of insulin actions, we have studied how insulin activates STAT proteins in Hep3B cells. Insulin rapidly phosphorylated Stat1alpha at tyrosine residues and increased its specific binding activities to a GAS/ISRE consensus oligonucleotide. IL-4 also phosphorylated Stat1alpha and increased DNA binding activities to the same Stat1alpha responsive element. There was no increase in tyrosine phosphorylation of JAK family of kinases following insulin stimulation. In contrast, IL-4 stimulated tyrosine phosphorylation of JAK1, JAK2 and tyk2 in this cell line. These data indicate that insulin receptor signaling can activate the transcriptional regulatory function of STAT protein, and that insulin actions on Stat1alpha are mediated through signaling pathways independent of JAK family of kinases.
Chuang
L M
LM
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
Wang
P H
PH
Chang
H M
HM
Lee
S C
SC
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D050832:Interferon-Stimulated Gene Factor 3; D015847:Interleukin-4 / Q000494:pharmacology; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D003854:Deoxyribonucleotides; D007328:Insulin; D050832:Interferon-Stimulated Gene Factor 3; D009687:Nuclear Proteins; D014157:Transcription Factors; C079868:gamma interferon activation factor; D015847:Interleukin-4; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases