NOVEL PATHWAY OF INSULIN SIGNALING INVOLVING STAT1-ALPHA IN HEP3B CELLS

STAT proteins are important transcription factors that regulate cell g rowth and differentiation. To elucidate the molecular mechanisms of in sulin actions, we have studied how insulin activates STAT proteins in Hep3B cells. Insulin rapidly phosphorylated Stat1 alpha at tyrosine re sidues and increased its specific binding activities to a GAS/ISRE con sensus oligonucleotide, IL-4 also phosphorylated Stat1 alpha and incre ased DNA binding activities to the same Stat1 alpha responsive element . There was no increase in tyrosine phosphorylation of JAK family of k inases following insulin stimulation, In contrast, IL-4 stimulated tyr osine phosphorylation of JAK1, JAK2 and tyk2 in this cell line. These data indicate that insulin receptor signaling can activate the transcr iptional regulatory function of STAT protein, and that insulin actions on Stat1 alpha are mediated through signaling pathways independent of JAK family of kinases. (C) 1997 Academic Press.