The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform

Jerome A. Langer - One of the best experts on this subject based on the ideXlab platform.

  • Cloning and characterization of a bovine Alpha Interferon Receptor.
    Biochimica et biophysica acta, 1993
    Co-Authors: Jinkyu Lim, Jerome A. Langer
    Abstract:

    Abstract A bovine Interferon α Receptor (BoIFN-αR1) cDNA, homologous to the human cDNA [1], was isolated. Transfection of the BoIFN-αR1 cDNA into monkey COS cells results in a large increase in high-affinity binding sites for human IFN-αA and IFN-αB. Covalent crosslinking of radiolabeled HuIFN-αA and -αB demonstrates that the complex of [ 32 P]HuIFN with the BoIFN-αR1 protein (predicted mass, 61375) expressed in COS cells migrates as a 140–150 kDa band.

Emilio Flano - One of the best experts on this subject based on the ideXlab platform.

  • local blockade of epithelial pdl 1 in the airways enhances t cell function and viral clearance during influenza virus infection
    Journal of Virology, 2013
    Co-Authors: Eth Mcnally, Meredith Willette, Emilio Flano
    Abstract:

    In order to maintain the gas exchange function of the lung following influenza virus infection, a delicate orchestration of positive and negative regulatory pathways must be maintained to attain viral eradication while minimizing local inflammation. The programmed death Receptor 1 ligand/programmed death Receptor 1 (PDL-1/PD-1) pathway plays an important immunoregulatory role, particularly in the context of T cell function. Here, we have shown that influenza virus infection of primary airway epithelial cells strongly enhances PDL-1 expression and does so in an Alpha Interferon Receptor (IFNAR) signaling-dependent manner. PD-1 is expressed primarily on effector T cells in the lung, compared to effector memory and central memory cells, and shortly after influenza virus infection, an increased number of PD-1+ T cells are recruited to the airways. Using in vitro cocultures of airway epithelial cells and T cells and in vivo models of influenza virus infection, we have demonstrated that blockade of airway epithelial PDL-1 improves CD8 T cell function, defined by increased production of gamma Interferon (IFN-γ) and granzyme B and expression of CD107ab. Furthermore, PDL-1 blockade in the airways served to accelerate influenza virus clearance and enhance infection recovery. Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection.

Jinkyu Lim - One of the best experts on this subject based on the ideXlab platform.

  • Cloning and characterization of a bovine Alpha Interferon Receptor.
    Biochimica et biophysica acta, 1993
    Co-Authors: Jinkyu Lim, Jerome A. Langer
    Abstract:

    Abstract A bovine Interferon α Receptor (BoIFN-αR1) cDNA, homologous to the human cDNA [1], was isolated. Transfection of the BoIFN-αR1 cDNA into monkey COS cells results in a large increase in high-affinity binding sites for human IFN-αA and IFN-αB. Covalent crosslinking of radiolabeled HuIFN-αA and -αB demonstrates that the complex of [ 32 P]HuIFN with the BoIFN-αR1 protein (predicted mass, 61375) expressed in COS cells migrates as a 140–150 kDa band.

John J. Krolewski - One of the best experts on this subject based on the ideXlab platform.

  • Molecular characterization of an Alpha Interferon Receptor 1 subunit (IFNaR1) domain required for TYK2 binding and signal transduction.
    Molecular and cellular biology, 1996
    Co-Authors: Hai Yan, Kartik Krishnan, J. T. E. Lim, L. G. Contillo, John J. Krolewski
    Abstract:

    Binding of Alpha Interferon (IFNa) 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.WealsoprovidedirectevidencethatthebindingregionisbothnecessaryandsufficienttoactivateTYK2 in vivo. Specifically, mutations in the binding domain act in a dominant-negative fashion to inhibit the IFNa-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 andtheReceptor,confirmingtheroleofthebindingdomaininIFNasignaltransduction.Thesestudiesprovide 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.

Nobuhiro Fujii - One of the best experts on this subject based on the ideXlab platform.

  • association of mumps virus v protein with rack1 results in dissociation of stat 1 from the Alpha Interferon Receptor complex
    Journal of Virology, 2002
    Co-Authors: Toru Kubota, Noriko Yokosawa, Shinichi Yokota, Nobuhiro Fujii
    Abstract:

    It has been reported that mumps virus protein V or the C-terminal Cys-rich region of protein V (Vsp) is associated with blocking of the Interferon (IFN) signal transduction pathway through a decrease in STAT-1 production. The intracellular target of the V protein was investigated by using a two-hybrid screening system with Vsp as bait. Full-length V protein and Vsp were able to bind to RACK1, and the interaction did not require two WD domains, WD1 and WD2, in RACK1. A significant interaction between V protein and RACK1 was also demonstrated in cells persistently infected with mumps virus (FLMT cells), and the formation of the complex was not affected by treatment with IFN. On the other hand, in uninfected cells, STAT-1 was associated with the long form of the β subunit of the Alpha IFN Receptor, and this association was mediated by the function of RACK1 as an adaptor protein. Immunoprecipitation and glutathione S -transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN Receptor was undetectable in mumps virus-infected cells. Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did. Therefore, it is suggested that mumps virus V protein has the ability to interact strongly with RACK1 and consequently to bring about the disruption of the complex formed from STAT-1, RACK1, and the IFN Receptor.