Ligand-induced assembly and activation of the gamma interferon receptor in intact cells

Erika A. Bach, J. William Tanner, Scot Marsters, Avi Ashkenazi, Michel Aguet, Andrey S. Shaw, Robert D. Schreiber

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Functionally active gamma interferon (IFN-γ) receptors consist of an α subunit required for ligand binding and signal transduction and a β subunit required primarily for signaling. Although the receptor α chain has been well characterized, little is known about the specific role of the receptor β chain in IFN-γ signaling. Expression of the wild-type human IFN-γ receptor β chain in murine L cells that stably express the human IFN-γ receptor α chain (L.hgR) produced a murine cell line (L.hgR.mycβ) that responded to human IFN-γ. Mutagenesis of the receptor β-chain intracellular domain revealed that only two closely spaced, membrane-proximal sequences (P263PSIP267 and I270EEYL274) are required for function. Coprecipitation studies showed that these sequences are necessary for the specific and constitutive association of the receptor β chain with the JAK- 2 tyrosine kinase. These experiments also revealed that the IFN-γ receptor α and β chains are not preassociated on the surface of unstimulated cells but rather are induced to associate in an IFN-γ-dependent fashion. A chimeric protein in which the intracellular domain of the β chain was replaced by JAK-2 complemented human IFN-γ signaling and biologic responsiveness in L.hgR. In contrast, a c-src-containing β-chain chimera did not. These results indicate that the sole obligate role of the IFN-γ receptor β chain in signaling is to recruit JAK-2 into the ligand-assembled receptor complex.

Original languageEnglish
Pages (from-to)3214-3221
Number of pages8
JournalMolecular and cellular biology
Issue number6
StatePublished - 1996


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