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Maya Kozlowski - One of the best experts on this subject based on the ideXlab platform.

  • il 6 production is positively regulated by two distinct Src Homology Domain 2 containing tyrosine phosphatase 1 shp 1 dependent ccaat enhancer binding protein β and nf κb pathways and an shp 1 independent nf κb pathway in lipopolysaccharide stimulate
    Journal of Immunology, 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

  • IL-6 Production Is Positively Regulated by Two Distinct Src Homology Domain 2-Containing Tyrosine Phosphatase-1 (SHP-1)–Dependent CCAAT/Enhancer-Binding Protein β and NF-κB Pathways and an SHP-1–Independent NF-κB Pathway in Lipopolysaccharide-Stimula
    Journal of immunology (Baltimore Md. : 1950), 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

Dorothy Rego - One of the best experts on this subject based on the ideXlab platform.

  • il 6 production is positively regulated by two distinct Src Homology Domain 2 containing tyrosine phosphatase 1 shp 1 dependent ccaat enhancer binding protein β and nf κb pathways and an shp 1 independent nf κb pathway in lipopolysaccharide stimulate
    Journal of Immunology, 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

  • IL-6 Production Is Positively Regulated by Two Distinct Src Homology Domain 2-Containing Tyrosine Phosphatase-1 (SHP-1)–Dependent CCAAT/Enhancer-Binding Protein β and NF-κB Pathways and an SHP-1–Independent NF-κB Pathway in Lipopolysaccharide-Stimula
    Journal of immunology (Baltimore Md. : 1950), 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

Ashok Kumar - One of the best experts on this subject based on the ideXlab platform.

  • il 6 production is positively regulated by two distinct Src Homology Domain 2 containing tyrosine phosphatase 1 shp 1 dependent ccaat enhancer binding protein β and nf κb pathways and an shp 1 independent nf κb pathway in lipopolysaccharide stimulate
    Journal of Immunology, 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

  • IL-6 Production Is Positively Regulated by Two Distinct Src Homology Domain 2-Containing Tyrosine Phosphatase-1 (SHP-1)–Dependent CCAAT/Enhancer-Binding Protein β and NF-κB Pathways and an SHP-1–Independent NF-κB Pathway in Lipopolysaccharide-Stimula
    Journal of immunology (Baltimore Md. : 1950), 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

Ladan Nilchi - One of the best experts on this subject based on the ideXlab platform.

  • il 6 production is positively regulated by two distinct Src Homology Domain 2 containing tyrosine phosphatase 1 shp 1 dependent ccaat enhancer binding protein β and nf κb pathways and an shp 1 independent nf κb pathway in lipopolysaccharide stimulate
    Journal of Immunology, 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

  • IL-6 Production Is Positively Regulated by Two Distinct Src Homology Domain 2-Containing Tyrosine Phosphatase-1 (SHP-1)–Dependent CCAAT/Enhancer-Binding Protein β and NF-κB Pathways and an SHP-1–Independent NF-κB Pathway in Lipopolysaccharide-Stimula
    Journal of immunology (Baltimore Md. : 1950), 2011
    Co-Authors: Dorothy Rego, Ashok Kumar, Ladan Nilchi, Kathryn E. Wright, Stephen Huang, Maya Kozlowski
    Abstract:

    Comparison of the inflammatory cytokine profile in bone marrow-derived macrophages (BMDMs) from normal and Src Homology Domain 2-containing tyrosine phosphatase-1 (SHP-1)–deficient Motheaten (me/me) mice revealed a dramatic suppression of IL-6 transcript and protein in me/me BMDMs after LPS stimulation. Interfering with SHP-1 expression using antisense SHP-1 oligonucleotides led to a significant downregulation of IL-6 in normal BMDMs. Conversely, reconstitution of me/me BMDMs with the SHP-1 gene using adenoviral vectors restored IL-6 production. Expression of only SHP-1 Src Homology region 2 Domains in normal BMDMs inhibited IL-6 production, confirming that IL-6 regulation depends on SHP-1 phosphatase activity. We further demonstrated that loss of SHP-1 function affects proper phosphorylation of Erk1/2 MAPKs and, to a lesser degree, of NF-κB downstream of TLR4 in BMDMs. Inefficient phosphorylation of Erk1/2 MAPKs abrogated the activation of C/EBPβ transcription factor, which was reversed on restoration of SHP-1 function and led to a concomitant enhancement of IL-6 production. We demonstrate that IL-6 production is regulated by a complex network of signaling pathways that include SHP-1–dependent activation of Erk1/2–C/EBPβ and NF-κB, in addition to SHP-1–independent IκB pathway through the activation of protein tyrosine kinases downstream of TLR4. Taken together, these results revealed for the first time, to our knowledge, a positive and critical role of SHP-1 in IL-6 regulation and dependence of Erk1/2–C/EBPβ pathway in addition to that of IκB on SHP-1 activity required for IL-6 induction after LPS stimulation.

Peer Bork - One of the best experts on this subject based on the ideXlab platform.

  • characterization of a novel protein binding module the ww Domain
    FEBS Letters, 1995
    Co-Authors: Marius Sudol, Henry I Chen, Cecile Bougeret, Aaron Einbond, Peer Bork
    Abstract:

    We have identified, characterized and cloned human, mouse and chicken cDNA of a novel protein that binds to the Src Homology Domain 3 (SH3) of the Yes proto-oncogene product. We subsequently named it YAP for Yes-associated protein. Analysis of the YAP sequence revealed a protein module that was found in various structural, regulatory and signaling molecules. Because one of the prominent features of this sequence motif is the presence of two conserved tryptophans (W), we named it the WW Domain. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW Domain of YAP which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous proline-rich region. Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW Domain of YAP, with a preliminary consensus that is different from the SH3-binding PXXP motif. This suggests that the WW Domain has a role in mediating protein-protein interactions via proline-rich regions, similar but distinct from Src Homology 3 (SH3) Domains. Based on this finding, we hypothesize that additional protein modules exist and that they could be isolated using proline-rich peptides as functional probes.

  • Characterization of a novel protein-binding module — the WW Domain
    FEBS Letters, 1995
    Co-Authors: Marius Sudol, Henry I Chen, Cecile Bougeret, Aaron Einbond, Peer Bork
    Abstract:

    We have identified, characterized and cloned human, mouse and chicken cDNA of a novel protein that binds to the Src Homology Domain 3 (SH3) of the Yes proto-oncogene product. We subsequently named it YAP for Yes-associated protein. Analysis of the YAP sequence revealed a protein module that was found in various structural, regulatory and signaling molecules. Because one of the prominent features of this sequence motif is the presence of two conserved tryptophans (W), we named it the WW Domain. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW Domain of YAP which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous proline-rich region. Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW Domain of YAP, with a preliminary consensus that is different from the SH3-binding PXXP motif. This suggests that the WW Domain has a role in mediating protein-protein interactions via proline-rich regions, similar but distinct from Src Homology 3 (SH3) Domains. Based on this finding, we hypothesize that additional protein modules exist and that they could be isolated using proline-rich peptides as functional probes.

  • Minireview Characterization of a novel protein-binding module - the WW Domain
    1995
    Co-Authors: Marius Sudol, Henry I Chen, Cecile Bougeret, Aaron Einbond, Peer Bork
    Abstract:

    We have identified, characterized and cloned human, mouse and chicken cDNA of a novel protein that binds to the Src Homology Domain 3 (SH3) of the Yes proto-oncogene product. We subsequently named it YAP for Yes-associated protein. Anal- ysis of the YAP sequence revealed a protein module that was found in various structural, regulatory and signaling molecules. Because one of the prominent features of this sequence motif is the presence of two conserved tryptophans (W), we named it the WW Domain. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW do- main of YAP which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous proline-rich region. Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW Domain of YAP, with a preliminary consensus that is different from the SH3- binding PXXP motif. This suggests that the WW Domain has a role in mediating protein-protein interactions via proline-rich regions, similar but distinct from Src Homology 3 (SH3) Domains. Based on this finding, we hypothesize that additional protein modules exist and that they could be isolated using proline-rich peptides as functional probes.