The human interferon $alpha;/$beta; receptor: Characterization and molecular cloning

Novick, Daniela; Cohen, Batya; Rubinstein, Menachem

doi:10.1016/0092-8674(94)90154-6

Cited by 619 publications

(337 citation statements)

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“…Rabbit polyclonal anti-human IFNAR2 antibody (OCT4813, Otsuka Pharmaceutical Co., Tokushima) and its blocking peptide were prepared according to the report by Novick et al (1994).…”

Section: Reagentsmentioning

confidence: 99%

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

et al. 2005

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We previously reported the beneficial effects of combination therapy of interferon (IFN)-a/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumour thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than double the number of patients relative to the original report, and evaluates the role of IFN-a/type 2 interferon receptor (IFNAR2) expression on the response to the combination therapy. The study subjects were 55 patients with advanced HCC and tumour thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least two courses of IFN-a/5-FU without major complication. In the 55 patients, 24 (43.6%) showed objective response (eight (14.5%) showed complete response, 16 (29.1%) partial response), four (7.3%) showed no response, and 27 (49.1%) showed progressive disease. Immunohistochemically, IFNAR2 expression was detected in nine out of 13 (69.2%) patients. There was significant difference in the time-to-progression survival (P ¼ 0.0002) and the overall survival (Po0.0001) between IFNAR2-positive and -negative cases. There was a significant correlation between IFNAR2 expression and response to IFN-a/5-FU combination therapy in univariate analysis (P ¼ 0.0070). IFN-a/5-FU combination therapy is a promising modality for advanced HCC with tumour thrombi in the major portal branches and could significantly depend on IFNAR2 expression.

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“…Rabbit polyclonal anti-human IFNAR2 antibody (OCT4813, Otsuka Pharmaceutical Co., Tokushima) and its blocking peptide were prepared according to the report by Novick et al (1994).…”

Section: Reagentsmentioning

confidence: 99%

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

et al. 2005

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“…Recently, a second cDNA for a human IFN-~R, here referred to as IFN-~R2, has been cloned and initially characterized [17]. This cDNA encodes both membranebound and soluble forms of an IFN receptor which has the intrinsic ability to bind several IFN-0cs and IFN-fl.…”

Section: Introductionmentioning

confidence: 99%

“…This cDNA encodes both membranebound and soluble forms of an IFN receptor which has the intrinsic ability to bind several IFN-0cs and IFN-fl. As with antibodies to IFN-~R1, antibodies to IFN-~R2 block the binding of a variety of Type I IFNs to human cells [17]. A multi-subunit structure for the IFN-~R is also indicated by the results of previous affinity crosslinking experiments, which show multiple bands representing complexes of cell surface proteins with HulFN-~s, and by the characterization of several monoclonal antibodies that appear to recognize cell surface polypeptides involved in Type I IFN-0~ binding [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic ligand binding properties of the human and bovine α,‐interferon receptors

et al. 1994

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The Type I interferon receptor (IFN-0~R) interacts with all IFN-~s, 1FN-~ and IFN-oL and seems to be a multisubunit receptor. To investigate the role of a cloned receptor subunit (IFN-aRI), we have examined the intrinsic ligand binding properties of the bovine and human IFN-~RI polypeptides expressed in Xenopus laevis oocytes. Albeit with different efficiencies, Xenopus oocytes expressing either the human or bovine IFN-~R1 polypeptide exhibit significant binding and formation of crosslinked complexes with human IFN-~A and IFN-~B. Thus, the IFN-c~R 1 polypeptide most likely plays a direct role in ligand binding.

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“…All human type I IFNs (IFN-␣, -␤, and -) bind to a cell surface receptor consisting of two transmembrane proteins, type I IFN receptor (ifnar) 1 (1) and ifnar2 (2), which associate upon binding. IFN binds with high affinity to ifnar2, probably recruiting ifnar1 subsequently.…”

mentioning

confidence: 99%

Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking

Roisman

Piehler

Trosset

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The pleiotropic activity of type I interferons has been attributed to the specific interaction of IFN with the cell-surface receptor components ifnar1 and ifnar2. To date, the structure of IFN has been solved, but not that of the receptor or the complex. In this study, the structure of the IFN-␣2-ifnar2 complex was generated with a docking procedure, using nuclear Overhauser effect-like distance constraints obtained from double-mutant cycle experiments. The interaction free energy between 13 residues of the ligand and 11 of the receptor was measured by double-mutant cycles. Of the 100 pairwise interactions probed, five pairs of residues were found to interact. These five interactions were incorporated as distance constraints into the flexible docking program PRODOCK by using fixed and movable energy-gradient grids attached to the receptor and ligand, respectively. Multistart minimization and Monte Carlo minimization docking of IFN-␣2 onto ifnar2 converged to a welldefined average structure, with the five distance constraints being satisfied. Furthermore, no structural artifacts or intraloop energy strain were observed. The mutual binding sites on IFN-␣2 and ifnar2 predicted from the model showed an almost complete superposition with the ones determined from mutagenesis studies. Based on this structure, differences in IFN-␣2 versus IFN-␤ binding are discussed.protein-protein interaction ͉ PRODOCK ͉ Monte Carlo minimization ͉ grids T ype I interferons (IFNs) are a family of homologous cytokines that potently elicit an antiviral and antiproliferative state in cells. All human type I IFNs (IFN-␣, -␤, and -) bind to a cell surface receptor consisting of two transmembrane proteins, type I IFN receptor (ifnar) 1 (1) and ifnar2 (2), which associate upon binding. IFN binds with high affinity to ifnar2, probably recruiting ifnar1 subsequently. Type I IFNs belong to the class of helical cytokines and are built of five helices. The structures of human IFN-␣2 (3) and IFN-␤ have been resolved (4). The receptor structures are unknown, but can be modeled by homology to human cytokine receptors with known structures such as tissue factor (5) and IFN-␥ receptor (6). Mutational studies have revealed the mutual binding sites on IFN-␣2 and ifnar2. On IFN-␣2, ifnar2 binds to the A helix (residues 12-15), the AB loop (residues 26-35), and the E helix (residues 144-153) (7), whereas on ifnar2, IFN-␣2 binds to three loops of the N-terminal domain of the receptor (residues 45-52, 75-82, and 102-106) with no significant binding detected toward the Cterminal domain (8-10). Determination of the receptor-ligand structure will significantly promote our understanding of IFN signaling at the molecular level.Docking of protein complexes, and calculating the conformational changes that occur at the binding interface, is a computational challenge. Rigid protein docking software algorithms are fast and can be used to dock two proteins for which the NMR or x-ray structures have been solved independently (11, 12). However, successful docking relies o...

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The human interferon $alpha;/$beta; receptor: Characterization and molecular cloning

Cited by 619 publications

References 45 publications

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

Intrinsic ligand binding properties of the human and bovine α,‐interferon receptors

Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking

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