The Jak Kinases Differentially Associate with the and (Accessory Factor) Chains of the Interferon Receptor to Form a Functional Receptor Unit Capable of Activating STAT Transcription Factors (*)

Interferon (IFN) induces the expression of early response genes by tyrosine phosphorylation of Jak kinases and transcription factors referred to as STAT proteins. The topology of the IFN receptor is partially understood and the relationship between the α chain that binds the ligand and the β chain that is required for signal transduction is undefined. In a cell line which expresses only the human α chain, we show that these cells did not activate Jak kinases or STAT proteins with human IFN, even though Jak1 co-immunoprecipitated with the α chain. In cells unexposed to IFN, Jak1 preferentially associated with the α chain, while Jak2 associated with the β chain. There was evidence for Jak1 kinase activity in untreated cells. For Jak2, kinase activity was IFN-dependent. Although the α chain was tyrosine-phosphorylated in response to ligand, we found no evidence for tyrosine phosphorylation of the β chain. These data are consistent with a model of the IFN receptor in which Jak1 associates with the α chain, whereas Jak2 associates with the β chain. IFN clusters at least two receptor units which results in the tyrosine phosphorylation of Jak1 and Jak2, the activation of Jak2 kinase activity, and the recruitment of STAT1α resulting in its activation by tyrosine phosphorylation.

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