Receptor Mediated Signaling

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Paul R Fallen - One of the best experts on this subject based on the ideXlab platform.

  • themis controls thymocyte selection through regulation of t cell antigen Receptor Mediated Signaling
    Nature Immunology, 2009
    Co-Authors: Guo Fu, Sebastien Vallee, Vasily Rybakin, Marielena V Mcguire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R Fallen
    Abstract:

    The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a Signaling protein essential for the positive selection of thymocytes.

  • themis controls thymocyte selection through regulation of t cell antigen Receptor Mediated Signaling
    Nature Immunology, 2009
    Co-Authors: Sebastien Vallee, Vasily Rybakin, Marielena V Mcguire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R Fallen, John A H Hoerter, Anil Munshi, Yina H Huang
    Abstract:

    Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen Receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR Signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.

Tsukasa Seya - One of the best experts on this subject based on the ideXlab platform.

  • ddx60 a dexd h box helicase is a novel antiviral factor promoting rig i like Receptor Mediated Signaling
    Molecular and Cellular Biology, 2011
    Co-Authors: Moeko Miyashita, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
    Abstract:

    The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2 but not to the downstream factors IPS-1 and IκB kinase e (IKK-e). Knockdown analysis shows that DDX60 is required for RIG-I- or MDA5-dependent type I interferon and interferon-inducible gene expression in response to viral infection. However, DDX60 is dispensable for TLR3-Mediated Signaling. Purified DDX60 helicase domains possess the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-stranded RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like Receptor-Mediated Signaling.

  • DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling
    Molecular and Cellular Biology, 2011
    Co-Authors: Moeko Miyashita, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
    Abstract:

    The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2 but not to the downstream factors IPS-1 and IκB kinase e (IKK-e). Knockdown analysis shows that DDX60 is required for RIG-I- or MDA5-dependent type I interferon and interferon-inducible gene expression in response to viral infection. However, DDX60 is dispensable for TLR3-Mediated Signaling. Purified DDX60 helicase domains possess the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-stranded RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like Receptor-Mediated Signaling.

  • DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling
    Molecular and Cellular Biology, 2011
    Co-Authors: Moeko Miyashita, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
    Abstract:

    The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2 but not to the downstream factors IPS-1 and IκB kinase e (IKK-e). Knockdown analysis shows that DDX60 is required for RIG-I- or MDA5-dependent type I interferon and interferon-inducible gene expression in response to viral infection. However, DDX60 is dispensable for TLR3-Mediated Signaling. Purified DDX60 helicase domains possess the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-stranded RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like Receptor-Mediated Signaling.

Tadashi Yamamoto - One of the best experts on this subject based on the ideXlab platform.

  • Physical and functional association of the cbl protooncogen product with an src-family protein tyrosine kinase, p53/56lyn, in the B cell antigen Receptor-Mediated Signaling.
    Journal of Experimental Medicine, 1996
    Co-Authors: Tohru Tezuka, Hisashi Umemori, Noemi Fusaki, T Yagi, M Takata, Tomohiro Kurosaki, Tadashi Yamamoto
    Abstract:

    To identify novel signal transducers involved in Signaling Mediated by the Src-family protein tyrosine kinases (PTKs), we used a yeast two-hybrid system with a probe corresponding to the regulatory region of p56lyn, a member of Src-family PTKs. One of the isolated clones contained the COOH-terminal 470 amino acid residues of p120c-cbl, the product of the cellular homologue of the v-cbl retroviral oncogene. p120c-cbl is a cytoplasmic protein with nuclear protein-like motifs. Here we show in vivo association of p120c-cbl with p53/56lyn. After stimulation of the B cell antigen Receptor (BCR), p120c-cbl was rapidly tyrosine phosphorylated. Studies with lyn- or syk-negative chicken B cells demonstrated that p53/56lyn, but not p72syk, was crucial for tyrosine phosphorylation of p120c-cbl upon stimulation of the BCR. We also show the importance of p59fyn in tyrosine phosphorylation of p120c-cbl in the T-cell Receptor-Mediated Signaling using fyn-overexpressing T cell hybridomas and splenic T cells from fyn-deficient mice. These results suggest that p120c-cbl is an important substrate of Src-family PTKs in the intracellular Signaling Mediated by the antigen Receptors

  • Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen Receptor-Mediated Signaling.
    Proceedings of the National Academy of Sciences, 1993
    Co-Authors: Yuji Yamanashi, Masato Okada, Toshihiko Semba, Takashi Yamori, Hisashi Umemori, Susumu Tsunasawa, Kumao Toyoshima, Daisuke Kitamura, Takeshi Watanabe, Tadashi Yamamoto
    Abstract:

    Abstract Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen Receptors, causes proliferation and differentiation of B cells or inhibition of their growth. The Receptor-Mediated Signaling involves tyrosine phosphorylation of cellular proteins and rapid activation of Src-like kinases. The amino acid sequences of five proteolytic peptides of p75, a major substrate of protein-tyrosine(s) in the Signaling, showed that p75 is the human HS1 gene product. The HS1 gene is expressed specifically in hematopoietic cells and encodes p75HS1, which carries both helix-turn-helix and Src homology 3 motifs. p75HS1 showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinases upon B-cell antigen Receptor-Mediated Signaling.

  • activation of src like protein tyrosine kinase lyn and its association with phosphatidylinositol 3 kinase upon b cell antigen Receptor Mediated Signaling
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Yuji Yamanashi, Kumao Toyoshima, Yasuhisa Fukui, Budsaba Wongsasant, Yumiko Kinoshita, Yuzo Ichimori, Tadashi Yamamoto
    Abstract:

    Abstract Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen Receptors, causes proliferation and differentiation of B cells or the inhibition of their growth. The Receptor-Mediated Signaling involves tyrosine phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is expressed preferentially in B cells and is an intracytoplasmic constituent of the B-cell antigen Receptor complex. Crosslinking of membrane-bound immunoglobulin M with antibody induced rapid increases in the kinase activities of Lyn and Lyn-associated phosphatidylinositol 3-kinase. Crosslinking of B-cell antigen Receptor also induced association of Lyn with an 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is functionally associated with membrane-bound immunoglobulin M and seems likely to participate in B-cell antigen Receptor-Mediated Signaling.

Antonio Pinto - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNA and Receptor Mediated Signaling pathways as potential therapeutic targets in heart failure.
    Expert Opinion on Therapeutic Targets, 2016
    Co-Authors: Antonino Tuttolomondo, Irene Simonetta, Antonio Pinto
    Abstract:

    ABSTRACTIntroduction: Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury.Areas covered: We will review recent advances in understanding the role of several Receptor-Mediated Signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various Receptor pathways), and other mechanisms Mediated by micro-RNAs. We will analyze the role of some Receptor Mediated Signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic Receptor subtypes and relaxin Receptor Signaling mechanisms, TNF/TNF Receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of hea...

  • MicroRNA and Receptor Mediated Signaling pathways as potential therapeutic targets in heart failure.
    Expert opinion on therapeutic targets, 2016
    Co-Authors: Antonino Tuttolomondo, Irene Simonetta, Antonio Pinto
    Abstract:

    Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several Receptor-Mediated Signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various Receptor pathways), and other mechanisms Mediated by micro-RNAs. We will analyze the role of some Receptor Mediated Signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic Receptor subtypes and relaxin Receptor Signaling mechanisms, TNF/TNF Receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of Receptor-Mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.

Marielena V Mcguire - One of the best experts on this subject based on the ideXlab platform.

  • themis controls thymocyte selection through regulation of t cell antigen Receptor Mediated Signaling
    Nature Immunology, 2009
    Co-Authors: Guo Fu, Sebastien Vallee, Vasily Rybakin, Marielena V Mcguire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R Fallen
    Abstract:

    The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a Signaling protein essential for the positive selection of thymocytes.

  • themis controls thymocyte selection through regulation of t cell antigen Receptor Mediated Signaling
    Nature Immunology, 2009
    Co-Authors: Sebastien Vallee, Vasily Rybakin, Marielena V Mcguire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R Fallen, John A H Hoerter, Anil Munshi, Yina H Huang
    Abstract:

    Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen Receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR Signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.