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Douglas J. Hilton - One of the best experts on this subject based on the ideXlab platform.
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Suppression of Cytokine Signaling: The SOCS perspective
Cytokine & growth factor reviews, 2013Co-Authors: Edmond M. Linossi, Douglas J. Hilton, Jeffrey J. Babon, Sandra E NicholsonAbstract:The discovery of the Suppressor of Cytokine Signaling (SOCS) family of proteins has resulted in a significant body of research dedicated to dissecting their biological functions and the molecular mechanisms by which they achieve potent and specific inhibition of Cytokine and growth factor Signaling. The Australian contribution to this field has been substantial, with the initial discovery of SOCS1 by Hilton, Starr and colleagues (discovered concurrently by two other groups) and the following work, providing a new perspective on the regulation of JAK/STAT Signaling. In this review, we reflect on the critical discoveries that have lead to our current understanding of how SOCS proteins function and discuss what we see as important questions for future research.
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The negative regulatory roles of suppressor of Cytokine Signaling proteins in myeloid Signaling pathways.
Current opinion in hematology, 2007Co-Authors: Sam Wormald, Douglas J. HiltonAbstract:PURPOSE OF REVIEW Suppressor of Cytokine Signaling proteins are key regulators of the response of myeloid cells to Cytokines and other extracellular stimuli. This review explores recent developments that have shed light on how two of the best-characterized suppressor of Cytokine Signaling proteins, SOCS1 and SOCS3, attenuate myeloid Signaling pathways that lead to inflammation, hematological malignancy, and related disorders. RECENT FINDINGS In addition to its 'classic' role as an inhibitor of IFNgamma Signaling, a number of new regulatory roles in IFNalpha and toll-like receptor Signaling have been defined for SOCS1, and substantial progress has been made in identifying the factors that give rise to lethal inflammation in Socs1 neonatal mice. The aberrant transcriptional regulation of suppressor of Cytokine Signaling genes in myeloid leukemia and related proliferative disorders has also been further defined. Finally, positive signs have emerged in mice that exogenous delivery of SOCS3 may be of therapeutic value. SUMMARY Suppressor of Cytokine Signaling proteins have pivotal roles in attenuating Cytokine and toll-like receptor Signaling in myeloid cells. Understanding how defective suppressor of Cytokine Signaling activity contributes to inflammatory and malignant disease promises to create significant new therapeutic opportunities.
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The comparative roles of suppressor of Cytokine Signaling-1 and -3 in the inhibition and desensitization of Cytokine Signaling.
The Journal of biological chemistry, 2006Co-Authors: Sam Wormald, Nicos A. Nicola, Jian-guo Zhang, Danielle L. Krebs, Lisa A. Mielke, Jeremy D. Silver, Warren S. Alexander, Terence P. Speed, Douglas J. HiltonAbstract:Abstract Negative feedback is a mechanism commonly employed in biological processes as a means of maintaining homeostasis. We have investigated the roles of suppressor of Cytokine Signaling (SOCS) proteins in regulating the kinetics of negative feedback in response to Cytokine Signaling. In mouse livers and bone marrow-derived macrophages, both interferon-γ (IFNγ) and interleukin-6 (IL-6) rapidly induced the tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT1) and STAT3. STAT3 tyrosine phosphorylation was bi-phasic in response to continuous IL-6 Signaling. In macrophages lacking Socs3, however, continuous IL-6 Signaling induced uniformly high levels of STAT3 tyrosine phosphorylation, and early IL-6-inducible genes were inappropriately expressed at intermediate time points. SOCS3 therefore imposes bi-phasic kinetics upon IL-6 Signaling. Compared with Socs3 mRNA, Socs1 mRNA was induced relatively slowly, and SOCS1 simply attenuated the duration of IFNγ Signaling. Surprisingly, heightened Socs1 mRNA expression but minimal STAT1 tyrosine phosphorylation was observed after prolonged stimulation with IFNγ, indicating that STAT1 may not play a large role in inducing Socs1 mRNA during steady-state IFNγ Signaling. We also demonstrate that both SOCS1 and SOCS3 can desensitize primary bone marrow-derived macrophages to IFNγ and IL-6 Signaling, respectively. Consistent with the kinetics with which Socs1 and Socs3 mRNAs were induced, SOCS3 desensitized cells to IL-6 rapidly, whereas SOCS1-mediated desensitization to IFNγ occurred at later time points. The kinetics with which SOCS proteins are induced by Cytokine may therefore be a parameter that is “hard-wired” into specific Cytokine Signaling pathways as a means of tailoring the kinetics with which cells become desensitized.
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suppressor of Cytokine Signaling 1 negatively regulates toll like receptor Signaling by mediating mal degradation
Nature Immunology, 2006Co-Authors: Ashley Mansell, Douglas J. Hilton, Rosealee Anne Smith, Sarah L Doyle, Pearl Gray, Jennifer Eve Fenner, Peter J Crack, Sandra E Nicholson, Luke A J Oneill, Paul J HertzogAbstract:Suppressor of Cytokine Signaling 1 negatively regulates Toll-like receptor Signaling by mediating Mal degradation
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suppressor of Cytokine Signaling 1 regulates the immune response to infection by a unique inhibition of type i interferon activity
Nature Immunology, 2006Co-Authors: Jennifer Eve Fenner, Douglas J. Hilton, Jian-guo Zhang, Robyn Starr, Ann L Cornish, Donald Metcalf, Robert D Schreiber, Kathleen C F Sheehan, Warren S. AlexanderAbstract:Suppressor of Cytokine Signaling 1 (SOCS1) is a critical regulator of Cytokine Signaling and immune responses. SOCS1-deficient mice develop severe inflammatory disease, but are very resistant to viral infections. Using neutralizing antibody to type I interferon (IFN-α and IFN-β) and mice deficient in interferon-γ or type I interferon receptor components (IFNAR1 or IFNAR2), we demonstrate here that SOCS1 deficiency amplified type I interferon antiviral and proinflammatory actions independently of interferon-γ. The mechanism of the suppression of type I interferon responses by SOCS1 was distinct from that of other Cytokines. SOCS1 associated with and regulated IFNAR1- but not IFNAR2-specific signals, abrogating tyrosine phosphorylation of transcription factor STAT1 and reducing the duration of antiviral gene expression. Thus, SOCS1 is an important in vivo inhibitor of type I interferon Signaling and contributes to balancing its beneficial antiviral versus detrimental proinflammatory effects on innate immunity.
Akihiko Yoshimura - One of the best experts on this subject based on the ideXlab platform.
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Negative Regulation of Cytokine Signaling in Immunity
Cold Spring Harbor perspectives in biology, 2018Co-Authors: Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko NakatsukasaAbstract:Cytokines are key modulators of immunity. Most Cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of Cytokine Signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate Cytokine signals that control the polarization of CD4+ T cells and the maturation of CD8+ T cells. SOCS proteins also regulate innate immune cells and are involved in tumorigenesis. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in T cells and tumor immunity.
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suppressors of Cytokine Signaling socs proteins and jak stat pathways regulation of t cell inflammation by socs1 and socs3
Arteriosclerosis Thrombosis and Vascular Biology, 2011Co-Authors: Taiga Tamiya, Hideo Yasukawa, Ikko Kashiwagi, Reiko Takahashi, Akihiko YoshimuraAbstract:Various Cytokines are involved in the regulation of the immune system and inflammation. Dysregulation of Cytokine Signaling can cause a variety of diseases, including allergy, autoimmune diseases, inflammation, and cancer. Most Cytokines use the so-called janus kinase/signal transducer and activator of transcription pathway, and this pathway is negatively regulated by suppressors of Cytokine Signaling (SOCS) proteins. SOCS proteins bind to janus kinase and to certain Cytokine receptors and Signaling molecules, thereby suppressing further Signaling events. Studies have shown that SOCS proteins are key physiological regulators of inflammation. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of adaptive immunity.
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Regulation of Cytokine Signaling by the SOCS and Spred family proteins.
The Keio journal of medicine, 2009Co-Authors: Akihiko YoshimuraAbstract:Various Cytokines are involved in the regulation of the immune system and of hematopoiesis. Most Cytokines utilize the so-called JAK-STAT pathway, but others activate the Ras-ERK pathway, which is more important than the STAT pathway for the proliferation of hematopoietic cells. Dysregulation of Cytokine Signaling can cause a variety of diseases, including allergy, inflammation, and cancer. We have identified two important regulator families involved in Cytokine Signaling: the SOCS proteins and the Spred proteins. Suppressors of Cytokine Signaling (SOCS) proteins bind to JAK and to certain receptors, thereby suppressing further Signaling events. Spred family proteins interact with Ras and Raf, thereby suppressing ERK activation. Studies have shown that SOCS and Spred proteins are key physiological regulators of immunity, hematopoiesis, and angiogenesis. Evidence is also emerging for the involvement of these proteins in human diseases.
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Negative regulation of Cytokine Signaling.
Clinical reviews in allergy & immunology, 2005Co-Authors: Akihiko YoshimuraAbstract:Immune and inflammatory systems are controlled by multiple Cytokines, including interleukins and interferons. Many of these Cytokines exert their biological functions through Janus kinases and signal transducers and activators of transcription factors. The Cytokine-inducible SH2 protein (CIS) and suppressors of Cytokine Signaling (SOCS) are members of a family of intracellular proteins, several of which have emerged as key physiological regulators of Cytokine-mediated homeostasis, including innate and adaptive immunity. This article focuses on the molecular mechanism of the action of CIS/SOCS family proteins and their roles in immune regulation and inflammatory diseases.
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Suppressors of Cytokine Signaling and immunity
Nature immunology, 2003Co-Authors: Masato Kubo, Toshikatsu Hanada, Akihiko YoshimuraAbstract:The suppressors of Cytokine Signaling (SOCS) and Cytokine-inducible SH2 protein are key physiological regulators of the immune system. Principally, SOCS1 and SOCS3 regulate T cells as well as antigen-presenting cells, including macrophages and dendritic cells. Here we review the function of SOCS1 and SOCS3 in innate and adaptive immunity, with particular emphasis on the relationship between immune regulation and SOCS.
Warren S. Alexander - One of the best experts on this subject based on the ideXlab platform.
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The comparative roles of suppressor of Cytokine Signaling-1 and -3 in the inhibition and desensitization of Cytokine Signaling.
The Journal of biological chemistry, 2006Co-Authors: Sam Wormald, Nicos A. Nicola, Jian-guo Zhang, Danielle L. Krebs, Lisa A. Mielke, Jeremy D. Silver, Warren S. Alexander, Terence P. Speed, Douglas J. HiltonAbstract:Abstract Negative feedback is a mechanism commonly employed in biological processes as a means of maintaining homeostasis. We have investigated the roles of suppressor of Cytokine Signaling (SOCS) proteins in regulating the kinetics of negative feedback in response to Cytokine Signaling. In mouse livers and bone marrow-derived macrophages, both interferon-γ (IFNγ) and interleukin-6 (IL-6) rapidly induced the tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT1) and STAT3. STAT3 tyrosine phosphorylation was bi-phasic in response to continuous IL-6 Signaling. In macrophages lacking Socs3, however, continuous IL-6 Signaling induced uniformly high levels of STAT3 tyrosine phosphorylation, and early IL-6-inducible genes were inappropriately expressed at intermediate time points. SOCS3 therefore imposes bi-phasic kinetics upon IL-6 Signaling. Compared with Socs3 mRNA, Socs1 mRNA was induced relatively slowly, and SOCS1 simply attenuated the duration of IFNγ Signaling. Surprisingly, heightened Socs1 mRNA expression but minimal STAT1 tyrosine phosphorylation was observed after prolonged stimulation with IFNγ, indicating that STAT1 may not play a large role in inducing Socs1 mRNA during steady-state IFNγ Signaling. We also demonstrate that both SOCS1 and SOCS3 can desensitize primary bone marrow-derived macrophages to IFNγ and IL-6 Signaling, respectively. Consistent with the kinetics with which Socs1 and Socs3 mRNAs were induced, SOCS3 desensitized cells to IL-6 rapidly, whereas SOCS1-mediated desensitization to IFNγ occurred at later time points. The kinetics with which SOCS proteins are induced by Cytokine may therefore be a parameter that is “hard-wired” into specific Cytokine Signaling pathways as a means of tailoring the kinetics with which cells become desensitized.
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suppressor of Cytokine Signaling 1 regulates the immune response to infection by a unique inhibition of type i interferon activity
Nature Immunology, 2006Co-Authors: Jennifer Eve Fenner, Douglas J. Hilton, Jian-guo Zhang, Robyn Starr, Ann L Cornish, Donald Metcalf, Robert D Schreiber, Kathleen C F Sheehan, Warren S. AlexanderAbstract:Suppressor of Cytokine Signaling 1 (SOCS1) is a critical regulator of Cytokine Signaling and immune responses. SOCS1-deficient mice develop severe inflammatory disease, but are very resistant to viral infections. Using neutralizing antibody to type I interferon (IFN-α and IFN-β) and mice deficient in interferon-γ or type I interferon receptor components (IFNAR1 or IFNAR2), we demonstrate here that SOCS1 deficiency amplified type I interferon antiviral and proinflammatory actions independently of interferon-γ. The mechanism of the suppression of type I interferon responses by SOCS1 was distinct from that of other Cytokines. SOCS1 associated with and regulated IFNAR1- but not IFNAR2-specific signals, abrogating tyrosine phosphorylation of transcription factor STAT1 and reducing the duration of antiviral gene expression. Thus, SOCS1 is an important in vivo inhibitor of type I interferon Signaling and contributes to balancing its beneficial antiviral versus detrimental proinflammatory effects on innate immunity.
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the role of suppressors of Cytokine Signaling socs proteins in regulation of the immune response
Annual Review of Immunology, 2004Co-Authors: Warren S. Alexander, Douglas J. HiltonAbstract:▪ Abstract Cytokines are an integral component of the adaptive and innate immune responses. The Signaling pathways triggered by the engagement of Cytokines with their specific cell surface receptors have been extensively studied and have provided a profound understanding of the intracellular machinery that translates exposure of cells to Cytokine to a coordinated biological response. It has also become clear that cells have evolved sophisticated mechanisms to prevent excessive responses to Cytokines. In this review we focus on the suppressors of Cytokine Signaling (SOCS) family of cytoplasmic proteins that completes a negative feedback loop to attenuate signal transduction from Cytokines that act through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. SOCS proteins inhibit components of the Cytokine Signaling cascade via direct binding or by preventing access to the Signaling complex. The SOCS proteins also appear to target signal transducers for proteasomal destructi...
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Negative regulators of Cytokine Signaling.
International journal of hematology, 2001Co-Authors: Benjamin T. Kile, Nicos A. Nicola, Warren S. AlexanderAbstract:The interaction of a Cytokine with its specific cell surface receptor triggers the activation of intracellular Signaling pathways that ultimately program the cellular response. Although the specific components and actions of the pathways driving these responses, such as the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, are relatively well defined, it is becoming clear that important mechanisms exist to restrain these Signaling cascades.This review discusses the key biochemical actions and biological roles of the phosphatase SHP-1, the protein inhibitors of activated STATs (PIAS) and the suppressor of Cytokine Signaling (SOCS) protein family in the negative regulation of Cytokine signal transduction.
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liver degeneration and lymphoid deficiencies in mice lacking suppressor of Cytokine Signaling 1
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Robyn Starr, Douglas J. Hilton, Nicos A. Nicola, Donald Metcalf, Andrew G Elefanty, Marta Brysha, Tracy A Willson, Warren S. AlexanderAbstract:SOCS-1, a member of the suppressor of Cytokine Signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by Cytokines, and the protein binds and inhibits Janus kinases and reduces Cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from Cytokine receptors. To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein. SOCS-1−/− mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1−/− mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival.
Nicos A. Nicola - One of the best experts on this subject based on the ideXlab platform.
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suppressor of Cytokine Signaling 4 socs4 protects against severe Cytokine storm and enhances viral clearance during influenza infection
PLOS Pathogens, 2014Co-Authors: Lukasz Kedzierski, Nicos A. Nicola, Edmond M. Linossi, Donald Metcalf, Tatiana Kolesnik, Idie E Day, Nicola L Ird, Enjami T Kile, Gabrielle T Elz, Katherine KedzierskaAbstract:Suppressor of Cytokine Signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory Cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.
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The comparative roles of suppressor of Cytokine Signaling-1 and -3 in the inhibition and desensitization of Cytokine Signaling.
The Journal of biological chemistry, 2006Co-Authors: Sam Wormald, Nicos A. Nicola, Jian-guo Zhang, Danielle L. Krebs, Lisa A. Mielke, Jeremy D. Silver, Warren S. Alexander, Terence P. Speed, Douglas J. HiltonAbstract:Abstract Negative feedback is a mechanism commonly employed in biological processes as a means of maintaining homeostasis. We have investigated the roles of suppressor of Cytokine Signaling (SOCS) proteins in regulating the kinetics of negative feedback in response to Cytokine Signaling. In mouse livers and bone marrow-derived macrophages, both interferon-γ (IFNγ) and interleukin-6 (IL-6) rapidly induced the tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT1) and STAT3. STAT3 tyrosine phosphorylation was bi-phasic in response to continuous IL-6 Signaling. In macrophages lacking Socs3, however, continuous IL-6 Signaling induced uniformly high levels of STAT3 tyrosine phosphorylation, and early IL-6-inducible genes were inappropriately expressed at intermediate time points. SOCS3 therefore imposes bi-phasic kinetics upon IL-6 Signaling. Compared with Socs3 mRNA, Socs1 mRNA was induced relatively slowly, and SOCS1 simply attenuated the duration of IFNγ Signaling. Surprisingly, heightened Socs1 mRNA expression but minimal STAT1 tyrosine phosphorylation was observed after prolonged stimulation with IFNγ, indicating that STAT1 may not play a large role in inducing Socs1 mRNA during steady-state IFNγ Signaling. We also demonstrate that both SOCS1 and SOCS3 can desensitize primary bone marrow-derived macrophages to IFNγ and IL-6 Signaling, respectively. Consistent with the kinetics with which Socs1 and Socs3 mRNAs were induced, SOCS3 desensitized cells to IL-6 rapidly, whereas SOCS1-mediated desensitization to IFNγ occurred at later time points. The kinetics with which SOCS proteins are induced by Cytokine may therefore be a parameter that is “hard-wired” into specific Cytokine Signaling pathways as a means of tailoring the kinetics with which cells become desensitized.
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The Jak-Stat Pathway of Cytokine Signaling
Hematopoietic Growth Factors in Oncology, 2004Co-Authors: Ben A. Croker, Nicos A. NicolaAbstract:Hematopoiesis is defined by progressive changes in Cytokine receptor expression and a delicate balance of intracellular activators and negative regulators of Cytokine Signaling. Binding of Cytokines to their cognate receptors activates downstream Signaling pathways and induces biologic responses. The plethora of Cytokines that exhibit common structural motifs and use common receptor subunits and Signaling pathways supports the notion of a highly redundant system. Mutation or deletion of components of these Cytokine-Signaling pathways, however, have defined remarkably specific roles for some Signaling elements in hematopoiesis and shown their importance in cell survival, proliferation, differentiation, and responses to infection, as well as their potential roles in tumorigenesis.
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Negative regulators of Cytokine Signaling.
International journal of hematology, 2001Co-Authors: Benjamin T. Kile, Nicos A. Nicola, Warren S. AlexanderAbstract:The interaction of a Cytokine with its specific cell surface receptor triggers the activation of intracellular Signaling pathways that ultimately program the cellular response. Although the specific components and actions of the pathways driving these responses, such as the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, are relatively well defined, it is becoming clear that important mechanisms exist to restrain these Signaling cascades.This review discusses the key biochemical actions and biological roles of the phosphatase SHP-1, the protein inhibitors of activated STATs (PIAS) and the suppressor of Cytokine Signaling (SOCS) protein family in the negative regulation of Cytokine signal transduction.
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liver degeneration and lymphoid deficiencies in mice lacking suppressor of Cytokine Signaling 1
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Robyn Starr, Douglas J. Hilton, Nicos A. Nicola, Donald Metcalf, Andrew G Elefanty, Marta Brysha, Tracy A Willson, Warren S. AlexanderAbstract:SOCS-1, a member of the suppressor of Cytokine Signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by Cytokines, and the protein binds and inhibits Janus kinases and reduces Cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from Cytokine receptors. To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein. SOCS-1−/− mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1−/− mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival.
Sandra E Nicholson - One of the best experts on this subject based on the ideXlab platform.
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kinase inhibition competitive binding and proteasomal degradation resolving the molecular function of the suppressor of Cytokine Signaling socs proteins
Immunological Reviews, 2015Co-Authors: Edmond M. Linossi, Sandra E NicholsonAbstract:Summary The suppressor of Cytokine Signaling (SOCS) family of proteins are key negative regulators of Cytokine and growth factor Signaling. They act at the receptor complex to modulate the intracellular Signaling cascade, preventing excessive Signaling and restoring homeostasis. This regulation is critical to the normal cessation of Signaling, highlighted by the complex inflammatory phenotypes exhibited by mice deficient in SOCS1 or SOCS3. These two SOCS proteins remain the best characterized of the eight family members (CIS, SOCS1-7), and in particular, we now possess a sound understanding of the mechanism of action for SOCS3. Here, we review the mechanistic role of the SOCS proteins and identify examples where clear, definitive data have been generated and discuss areas where the information is less clear. From this functional viewpoint, we discuss how the SOCS proteins achieve exquisite and specific regulation of Cytokine Signaling and highlight outstanding questions regarding the function of the less well-studied SOCS family members.
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Suppression of Cytokine Signaling: The SOCS perspective
Cytokine & growth factor reviews, 2013Co-Authors: Edmond M. Linossi, Douglas J. Hilton, Jeffrey J. Babon, Sandra E NicholsonAbstract:The discovery of the Suppressor of Cytokine Signaling (SOCS) family of proteins has resulted in a significant body of research dedicated to dissecting their biological functions and the molecular mechanisms by which they achieve potent and specific inhibition of Cytokine and growth factor Signaling. The Australian contribution to this field has been substantial, with the initial discovery of SOCS1 by Hilton, Starr and colleagues (discovered concurrently by two other groups) and the following work, providing a new perspective on the regulation of JAK/STAT Signaling. In this review, we reflect on the critical discoveries that have lead to our current understanding of how SOCS proteins function and discuss what we see as important questions for future research.
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suppressor of Cytokine Signaling 1 negatively regulates toll like receptor Signaling by mediating mal degradation
Nature Immunology, 2006Co-Authors: Ashley Mansell, Douglas J. Hilton, Rosealee Anne Smith, Sarah L Doyle, Pearl Gray, Jennifer Eve Fenner, Peter J Crack, Sandra E Nicholson, Luke A J Oneill, Paul J HertzogAbstract:Suppressor of Cytokine Signaling 1 negatively regulates Toll-like receptor Signaling by mediating Mal degradation
