Cloning and characterization of a bovine alpha interferon receptor

Lim, Jin Kyu; Langer, Jerome A.

doi:10.1016/0167-4781(93)90129-2

Cited by 23 publications

(31 citation statements)

References 28 publications

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“…These results are in accordance with previous studies, showing that high-level expression of HuIFNAR does not provide binding sites for IFN-␣ B (8,14). The increased (10- We found that the levels of antiviral activity and the induction of luciferase activity by IFN-␣ B in murine cells expressing both IFNAR and IFN-␣/␤R were lower than those detected in their parental cells, which express IFNAR only (Tables 1 and 2).…”

Section: Discussionsupporting

confidence: 80%

Ligand-Induced Association of the Type I Interferon Receptor Components

Cohen

Novick

Barak

et al. 1995

Molecular and Cellular Biology

160

109

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Section: Discussionsupporting

confidence: 80%

Ligand-Induced Association of the Type I Interferon Receptor Components

Cohen

Novick

Barak

et al. 1995

Molecular and Cellular Biology

160

109

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“…However, the GM-CSF receptor, which also binds JAK1, does contain a box 1 sequence which is required for binding (37). Finally, the murine and bovine IFNaR1 proteins both contain additional proline residues relative to the human homolog in the box 1-like region (26,48). Apparently these prolines are not required for binding.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of an Alpha Interferon Receptor 1 Subunit (IFNaR1) Domain Required for TYK2 Binding and Signal Transduction

Yan

Krishnan

Lim

et al. 1996

Molecular and Cellular Biology

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Binding of alpha interferon (IFN␣) to its receptors induces rapid tyrosine phosphorylation of the receptor subunits IFNaR1 and IFNaR2, the TYK2 and JAK1 tyrosine kinases, and the Stat1 and Stat2 transcription factors. Previous studies have demonstrated that TYK2 directly and specifically binds to and tyrosine phosphorylates IFNaR1 in vitro. We now report a detailed analysis of the TYK2 binding domain on the IFNaR1 subunit. First, we used an in vitro binding assay to identify the TYK2 binding motif in IFNaR1 as well as the critical residues within this region. The most striking feature is the importance of a number of hydrophobic and acidic residues. A minor role is also ascribed to a region resembling the proline-rich ''box 1'' sequence. In addition, mutations which disrupt in vitro binding also disrupt the coimmunoprecipitation of the receptor and TYK2. We also provide direct evidence that the binding region is both necessary and sufficient to activate TYK2 in vivo. Specifically, mutations in the binding domain act in a dominant-negative fashion to inhibit the IFN␣-induced tyrosine phosphorylation of TYK2 and Stat2. Further, introduction of dimerized glutathione S-transferase-IFNaR1 fusion proteins into permeabilized cells is sufficient to induce phosphorylation of TYK2 and the receptor, confirming the role of the binding domain in IFN␣ signal transduction. These studies provide clues to the sequences determining the specificity of the association between JAK family tyrosine kinases and cytokine receptors as well as the functional role of these kinases in cytokine signal transduction.A number of polypeptide hormones initiate signal transduction by binding to their cognate receptors and stimulating intracellular protein tyrosine kinase activity (43). Although cytokine receptors do not possess intrinsic tyrosine kinase activity, rapid tyrosine phosphorylation occurs in response to cytokine treatment of cells (reviewed in references 10, 22, 40, and 46). In a number of cases, JAK family tyrosine kinases are found associated with cytokine receptors and become activated following ligand binding (3,8,54). The JAKs are a structurally distinct subfamily of nonreceptor tyrosine kinases composed of TYK2 (14), JAK1 (53), JAK2 (19), JAK3 (6,23,39,45,55), and the gene product of the Drosophila hopscotch locus (5). These kinases are proteins of 115 to 135 kDa that contain a bona fide carboxy-terminal kinase domain along with an adjacent kinase-like domain and lack both SH2 and SH3 domains. The kinase-like domain contains a number of the sequence motifs characteristic of protein kinases but lacks some of the conserved amino acids thought to be essential for protein kinase activity (18). The amino-terminal half of the JAK kinases contains five additional regions of homology and a relatively unique region present at the extreme amino terminus of the protein (19,55). Some of these amino-terminal domains are apparently involved in the association of the JAKs with members of the cytokine receptor superfamily (47, 58). However, ther...

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“…This appears to reflect the ability of bovine IFNAR-1 (BoIFNAR-1) to bind human type I IFNs with moderately high affinity. Thus, human or murine cells expressing BoIFNAR-1 greatly increase their responsiveness to a variety of human type I IFNs (18,47,48). The nanomolar binding affinity of BoIFNAR-1 for HuIFN-␣s provides an elegant way to circumvent difficulties in the studies of the human IFN type I receptor complex (47)(48)(49)(50).…”

mentioning

confidence: 99%