The Experts below are selected from a list of 122430 Experts worldwide ranked by ideXlab platform
Alain Mauviel - One of the best experts on this subject based on the ideXlab platform.
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Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad Signaling Downstream of TGF-β: implications for carcinogenesis
Oncogene, 2005Co-Authors: Delphine Javelaud, Alain MauvielAbstract:Transforming growth factor- β (TGF- β ) superfamily members signal via membrane-bound heteromeric serine–threonine kinase receptor complexes. Upon ligand-binding, receptor activation leads to phosphorylation of cytoplasmic protein substrates of the Smad family. Following phosphorylation and oligomerization, the latter move into the nucleus to act as transcription factors to regulate target gene expression. TGF- β responses are not solely the result of the activation Smad cascade, but are highly cell-type specific and dependent upon interactions of Smad Signaling with a variety of other intracellular Signaling mechanisms, initiated or not by TGF- β itself, that may either potentiate, synergize, or antagonize, the rather linear TGF- β /Smad pathway. These include, (a), regulation of Smad activity by mitogen-activated protein kinases (MAPKs), (b), nuclear interaction of activated Smads with transcriptional cofactors, whether coactivators or corepressors, that may be themselves be regulated by diverse Signaling mechanisms, and (c), negative feedback loops exerted by inhibitory Smads, transcriptional targets of the Smad cascade. This review focuses on how MAPKs modulate the outcome of Smad activation by TGF- β , and how cross-Signaling mechanisms between the Smad and MAPK pathways may take place and affect cell fate in the context of carcinogenesis.
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crosstalk mechanisms between the mitogen activated protein kinase pathways and smad Signaling Downstream of tgf beta implications for carcinogenesis
Oncogene, 2005Co-Authors: Delphine Javelaud, Alain MauvielAbstract:Transforming growth factor-beta (TGF-beta) superfamily members signal via membrane-bound heteromeric serine-threonine kinase receptor complexes. Upon ligand-binding, receptor activation leads to phosphorylation of cytoplasmic protein substrates of the Smad family. Following phosphorylation and oligomerization, the latter move into the nucleus to act as transcription factors to regulate target gene expression. TGF-beta responses are not solely the result of the activation Smad cascade, but are highly cell-type specific and dependent upon interactions of Smad Signaling with a variety of other intracellular Signaling mechanisms, initiated or not by TGF-beta itself, that may either potentiate, synergize, or antagonize, the rather linear TGF-beta/Smad pathway. These include, (a), regulation of Smad activity by mitogen-activated protein kinases (MAPKs), (b), nuclear interaction of activated Smads with transcriptional cofactors, whether coactivators or corepressors, that may be themselves be regulated by diverse Signaling mechanisms, and (c), negative feedback loops exerted by inhibitory Smads, transcriptional targets of the Smad cascade. This review focuses on how MAPKs modulate the outcome of Smad activation by TGF-beta, and how cross-Signaling mechanisms between the Smad and MAPK pathways may take place and affect cell fate in the context of carcinogenesis.
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Control of connective tissue gene expression by TGF beta: role of Smad proteins in fibrosis.
Current Rheumatology Reports, 2002Co-Authors: Franck Verrecchia, Alain MauvielAbstract:Transforming growth factor-beta (TGF beta) plays a critical role in the development of tissue fibrosis. Its expression is consistently elevated in affected organs and correlates with increased extracellular matrix deposition. During the last few years, tremendous progress has been made in understanding the molecular aspects of intracellular Signaling Downstream of the TGF beta receptors. In particular, Smad proteins--TGF beta receptor kinase substrates that translocate into the cell nucleus to act as transcription factors--have been studied extensively. Their role in the modulation of extracellular matrix gene expression is discussed in this review.
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Control of connective tissue gene expression by TGFβ: Role of smad proteins in fibrosis
Current Rheumatology Reports, 2002Co-Authors: Franck Verrecchia, Alain MauvielAbstract:Transforming growth factor-beta (TGFβ) plays a critical role in the development of tissue fibrosis. Its expression is consistently elevated in affected organs and correlates with increased extracellular matrix deposition. During the last few years, tremendous progress has been made in understanding the molecular aspects of intracellular Signaling Downstream of the TGFβ receptors. In particular, Smad proteins—TGFβ receptor kinase substrates that translocate into the cell nucleus to act as transcription factors—have been studied extensively. Their role in the modulation of extracellular matrix gene expression is discussed in this review.
Makoto R Hara - One of the best experts on this subject based on the ideXlab platform.
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global phosphorylation analysis of β arrestin mediated Signaling Downstream of a seven transmembrane receptor 7tmr
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Kunhong Xiao, Jinpeng Sun, Jihee Kim, Sudarshan Rajagopal, Bo Zhai, Judit Villen, Wilhelm Haas, Jeffrey J Kovacs, Arun K Shukla, Makoto R HaraAbstract:β-Arrestin–mediated Signaling Downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for Signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the β-arrestin–biased ligand Sar1, Ile4, Ile8-angiotensin (SII), a ligand previously found to signal through β-arrestin–dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against Signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of β-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the β-arrestin–mediated phosphoproteome including construction of a kinase-substrate network for β-arrestin–mediated AT1aR Signaling. Our analysis demonstrates that β-arrestin–dependent Signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby β-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of β-arrestin–mediated phosphorylation events Downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR Signaling.
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Global phosphorylation analysis of β-arrestin–mediated Signaling Downstream of a seven transmembrane receptor (7TMR)
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Kunhong Xiao, Jinpeng Sun, Jihee Kim, Sudarshan Rajagopal, Bo Zhai, Judit Villen, Wilhelm Haas, Jeffrey J Kovacs, Arun K Shukla, Makoto R HaraAbstract:β-Arrestin–mediated Signaling Downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for Signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the β-arrestin–biased ligand Sar1, Ile4, Ile8-angiotensin (SII), a ligand previously found to signal through β-arrestin–dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against Signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of β-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the β-arrestin–mediated phosphoproteome including construction of a kinase-substrate network for β-arrestin–mediated AT1aR Signaling. Our analysis demonstrates that β-arrestin–dependent Signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby β-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of β-arrestin–mediated phosphorylation events Downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR Signaling.
Franck Verrecchia - One of the best experts on this subject based on the ideXlab platform.
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Control of connective tissue gene expression by TGF beta: role of Smad proteins in fibrosis.
Current Rheumatology Reports, 2002Co-Authors: Franck Verrecchia, Alain MauvielAbstract:Transforming growth factor-beta (TGF beta) plays a critical role in the development of tissue fibrosis. Its expression is consistently elevated in affected organs and correlates with increased extracellular matrix deposition. During the last few years, tremendous progress has been made in understanding the molecular aspects of intracellular Signaling Downstream of the TGF beta receptors. In particular, Smad proteins--TGF beta receptor kinase substrates that translocate into the cell nucleus to act as transcription factors--have been studied extensively. Their role in the modulation of extracellular matrix gene expression is discussed in this review.
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Control of connective tissue gene expression by TGFβ: Role of smad proteins in fibrosis
Current Rheumatology Reports, 2002Co-Authors: Franck Verrecchia, Alain MauvielAbstract:Transforming growth factor-beta (TGFβ) plays a critical role in the development of tissue fibrosis. Its expression is consistently elevated in affected organs and correlates with increased extracellular matrix deposition. During the last few years, tremendous progress has been made in understanding the molecular aspects of intracellular Signaling Downstream of the TGFβ receptors. In particular, Smad proteins—TGFβ receptor kinase substrates that translocate into the cell nucleus to act as transcription factors—have been studied extensively. Their role in the modulation of extracellular matrix gene expression is discussed in this review.
Delphine Javelaud - One of the best experts on this subject based on the ideXlab platform.
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Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad Signaling Downstream of TGF-β: implications for carcinogenesis
Oncogene, 2005Co-Authors: Delphine Javelaud, Alain MauvielAbstract:Transforming growth factor- β (TGF- β ) superfamily members signal via membrane-bound heteromeric serine–threonine kinase receptor complexes. Upon ligand-binding, receptor activation leads to phosphorylation of cytoplasmic protein substrates of the Smad family. Following phosphorylation and oligomerization, the latter move into the nucleus to act as transcription factors to regulate target gene expression. TGF- β responses are not solely the result of the activation Smad cascade, but are highly cell-type specific and dependent upon interactions of Smad Signaling with a variety of other intracellular Signaling mechanisms, initiated or not by TGF- β itself, that may either potentiate, synergize, or antagonize, the rather linear TGF- β /Smad pathway. These include, (a), regulation of Smad activity by mitogen-activated protein kinases (MAPKs), (b), nuclear interaction of activated Smads with transcriptional cofactors, whether coactivators or corepressors, that may be themselves be regulated by diverse Signaling mechanisms, and (c), negative feedback loops exerted by inhibitory Smads, transcriptional targets of the Smad cascade. This review focuses on how MAPKs modulate the outcome of Smad activation by TGF- β , and how cross-Signaling mechanisms between the Smad and MAPK pathways may take place and affect cell fate in the context of carcinogenesis.
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crosstalk mechanisms between the mitogen activated protein kinase pathways and smad Signaling Downstream of tgf beta implications for carcinogenesis
Oncogene, 2005Co-Authors: Delphine Javelaud, Alain MauvielAbstract:Transforming growth factor-beta (TGF-beta) superfamily members signal via membrane-bound heteromeric serine-threonine kinase receptor complexes. Upon ligand-binding, receptor activation leads to phosphorylation of cytoplasmic protein substrates of the Smad family. Following phosphorylation and oligomerization, the latter move into the nucleus to act as transcription factors to regulate target gene expression. TGF-beta responses are not solely the result of the activation Smad cascade, but are highly cell-type specific and dependent upon interactions of Smad Signaling with a variety of other intracellular Signaling mechanisms, initiated or not by TGF-beta itself, that may either potentiate, synergize, or antagonize, the rather linear TGF-beta/Smad pathway. These include, (a), regulation of Smad activity by mitogen-activated protein kinases (MAPKs), (b), nuclear interaction of activated Smads with transcriptional cofactors, whether coactivators or corepressors, that may be themselves be regulated by diverse Signaling mechanisms, and (c), negative feedback loops exerted by inhibitory Smads, transcriptional targets of the Smad cascade. This review focuses on how MAPKs modulate the outcome of Smad activation by TGF-beta, and how cross-Signaling mechanisms between the Smad and MAPK pathways may take place and affect cell fate in the context of carcinogenesis.
Kunhong Xiao - One of the best experts on this subject based on the ideXlab platform.
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global phosphorylation analysis of β arrestin mediated Signaling Downstream of a seven transmembrane receptor 7tmr
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Kunhong Xiao, Jinpeng Sun, Jihee Kim, Sudarshan Rajagopal, Bo Zhai, Judit Villen, Wilhelm Haas, Jeffrey J Kovacs, Arun K Shukla, Makoto R HaraAbstract:β-Arrestin–mediated Signaling Downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for Signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the β-arrestin–biased ligand Sar1, Ile4, Ile8-angiotensin (SII), a ligand previously found to signal through β-arrestin–dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against Signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of β-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the β-arrestin–mediated phosphoproteome including construction of a kinase-substrate network for β-arrestin–mediated AT1aR Signaling. Our analysis demonstrates that β-arrestin–dependent Signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby β-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of β-arrestin–mediated phosphorylation events Downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR Signaling.
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Global phosphorylation analysis of β-arrestin–mediated Signaling Downstream of a seven transmembrane receptor (7TMR)
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Kunhong Xiao, Jinpeng Sun, Jihee Kim, Sudarshan Rajagopal, Bo Zhai, Judit Villen, Wilhelm Haas, Jeffrey J Kovacs, Arun K Shukla, Makoto R HaraAbstract:β-Arrestin–mediated Signaling Downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for Signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the β-arrestin–biased ligand Sar1, Ile4, Ile8-angiotensin (SII), a ligand previously found to signal through β-arrestin–dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against Signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of β-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the β-arrestin–mediated phosphoproteome including construction of a kinase-substrate network for β-arrestin–mediated AT1aR Signaling. Our analysis demonstrates that β-arrestin–dependent Signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby β-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of β-arrestin–mediated phosphorylation events Downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR Signaling.
