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

https://doi.org/10.1074/jbc.270.29.17528Get rights and content
Under a Creative Commons license
open access

Interferon γ (IFNγ) 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 IFNγ 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 IFNγ, even though Jak1 co-immunoprecipitated with the α chain. In cells unexposed to IFNγ, 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 IFNγ-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 IFNγ receptor in which Jak1 associates with the α chain, whereas Jak2 associates with the β chain. IFNγ 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.

Cited by (0)

*

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

Current address: Human Genome Sciences, 9410 Key West Ave., Rockville, MD 20850.