Constitutive STAT1 tyrosine phosphorylation in U937 monocytes overexpressing the TYK2 protein tyrosine kinase does not induce gene transcription

Janus kinase (JAK) family protein tyrosine kinases are constituents of a signaling path leading to tyrosine phosphorylation and activation of signal transducer and activator of transcription (STAT) family transcription factors. IFN-cv activates two JAK family protein tyrosine kinases (TVK2 and JAKI) and two STAT family proteins (STAT1 and STAT2). We have generated a line of U937 promonocytes expressing a tyk2 transgene. 12-O-Tetradecanoylphothol-13acetate-mediated differentiation into monocytes resulted in transgene induction and both overexpression and constitutive activation of the kinase. -rvK2 protein in the transgenic line was found predominantly in a membrane fractiOn. Coprecipitation experiments demonstrated an association of constitutively tyrosine-phosphorylated TVK2 with the IFN-a receptor I chain. TYK2 activity led to an IFN-aindependent appearance of tyrosine-phosphorylated STATI but not STAT2 or JAKI proteins. Consistent with this, TYK2 activity also caused constitutive activation of the IFN-a-responsive transcription factor IFN-a activation factor, a dimer of tyrosinephosphorylated STATI, but not of the IFN-a-respons’ive