DOMINANT-NEGATIVE STAT3 MUTANT INHIBITS INTERLEUKIN-6-INDUCED JAK-STAT SIGNAL-TRANSDUCTION

Interleukin-6 (IL-6) induces tyrosine phosphorylation and activation o f the latent transcription factor Stat3 in HepG2 cells. Mutation of St at3 tyrosine 705 to phenylalanine (Y705F) inhibits IL-6-induced tyrosi ne phosphorylation of this Stat3 mutant in transfected HepG2 cells. In cotransfections of HepG2 cells, the Stat3 mutant Y705F causes a reduc tion of the tyrosine phosphorylation of wild type Stat3-FLAG. Moreover , Y705F inhibits the action of endogenous Stat3 in cotransfected cells , reducing IL-6 induction of a Stat3-responsive reporter construct. Y7 05F therefore acts as a dominant negative mutation of Stat3.