The Experts below are selected from a list of 43914 Experts worldwide ranked by ideXlab platform
Elizabeth K.k. Glennon - One of the best experts on this subject based on the ideXlab platform.
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alterations in phosphorylation of hepatocyte Ribosomal Protein S6 control plasmodium liver stage infection
Cell Reports, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan VijayanAbstract:Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.
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Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection
Elsevier, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan Vijayan, John D. Aitchison, Stefan H.i. Kappe, Alexis KaushanskyAbstract:Summary: Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection. : After mosquito-to-human transmission, Plasmodium parasites infect hepatocytes. Glennon et al. demonstrate that infected cells exhibit elevated levels of Ribosomal Protein S6 phosphorylation, and this phosphorylation appears uncoupled from canonical regulators. This work raises the possibility that Plasmodium-infected hepatocytes are governed by non-canonical, re-wired signal transduction cascades. Keywords: hepatocyte, Plasmodium, Ribosomal Protein S6, Toxoplasma, signal transductio
Fred D. Mast - One of the best experts on this subject based on the ideXlab platform.
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alterations in phosphorylation of hepatocyte Ribosomal Protein S6 control plasmodium liver stage infection
Cell Reports, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan VijayanAbstract:Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.
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Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection
Elsevier, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan Vijayan, John D. Aitchison, Stefan H.i. Kappe, Alexis KaushanskyAbstract:Summary: Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection. : After mosquito-to-human transmission, Plasmodium parasites infect hepatocytes. Glennon et al. demonstrate that infected cells exhibit elevated levels of Ribosomal Protein S6 phosphorylation, and this phosphorylation appears uncoupled from canonical regulators. This work raises the possibility that Plasmodium-infected hepatocytes are governed by non-canonical, re-wired signal transduction cascades. Keywords: hepatocyte, Plasmodium, Ribosomal Protein S6, Toxoplasma, signal transductio
Kamalakannan Vijayan - One of the best experts on this subject based on the ideXlab platform.
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alterations in phosphorylation of hepatocyte Ribosomal Protein S6 control plasmodium liver stage infection
Cell Reports, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan VijayanAbstract:Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.
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Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection
Elsevier, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan Vijayan, John D. Aitchison, Stefan H.i. Kappe, Alexis KaushanskyAbstract:Summary: Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection. : After mosquito-to-human transmission, Plasmodium parasites infect hepatocytes. Glennon et al. demonstrate that infected cells exhibit elevated levels of Ribosomal Protein S6 phosphorylation, and this phosphorylation appears uncoupled from canonical regulators. This work raises the possibility that Plasmodium-infected hepatocytes are governed by non-canonical, re-wired signal transduction cascades. Keywords: hepatocyte, Plasmodium, Ribosomal Protein S6, Toxoplasma, signal transductio
Rose Zamoyska - One of the best experts on this subject based on the ideXlab platform.
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mechanistic target of rapamycin complex 1 S6 kinase 1 signals influence t cell activation independently of Ribosomal Protein S6 phosphorylation
Journal of Immunology, 2015Co-Authors: Robert J Salmond, Oded Meyuhas, Rebecca J Brownlie, Rose ZamoyskaAbstract:Ag-dependent activation of naive T cells induces dramatic changes in cellular metabolism that are essential for cell growth, division, and differentiation. In recent years, the serine/threonine kinase mechanistic target of rapamycin (mTOR) has emerged as a key integrator of signaling pathways that regulate these metabolic processes. However, the role of specific downstream effectors of mTOR function in T cells is poorly understood. Ribosomal Protein S6 (rpS6) is an essential component of the ribosome and is inducibly phosphorylated following mTOR activation in eukaryotic cells. In the current work, we addressed the role of phosphorylation of rpS6 as an effector of mTOR function in T cell development, growth, proliferation, and differentiation using knockin and TCR transgenic mice. Surprisingly, we demonstrate that rpS6 phosphorylation is not required for any of these processes either in vitro or in vivo. Indeed, rpS6 knockin mice are completely sensitive to the inhibitory effects of rapamycin and an S6 kinase 1 (S6K1)–specific inhibitor on T cell activation and proliferation. These results place the mTOR complex 1-S6K1 axis as a crucial determinant of T cell activation independently of its ability to regulate rpS6 phosphorylation.
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mapk phosphatidylinositol 3 kinase and mammalian target of rapamycin pathways converge at the level of Ribosomal Protein S6 phosphorylation to control metabolic signaling in cd8 t cells
Journal of Immunology, 2009Co-Authors: Robert J Salmond, Juliet L Emery, Klaus Okkenhaug, Rose ZamoyskaAbstract:Ribosomal Protein S6 (rpS6) is a key component of the translational machinery in eukaryotic cells and is essential for ribosome biogenesis. rpS6 is phosphorylated on evolutionarily conserved serine residues, and data indicate that rpS6 phosphorylation might regulate cell growth and Protein synthesis. Studies in cell lines have shown an important role for the serine kinase mammalian target of rapamycin (mTOR) in rpS6 phosphorylation, further linking rpS6 to control of cellular metabolism. rpS6 is essential in T cells because its deletion in mouse double-positive thymocyte cells results in a complete block in T cell development; however, the signaling pathway leading to rpS6 phosphorylation downstream of TCR stimulation has yet to be fully characterized. We show that maximal TCR-induced rpS6 phosphorylation in CD8 T cells requires both Lck and Fyn activity and downstream activation of PI3K, mTOR, and MEK/ERK MAPK pathways. We demonstrate that there is cross-talk between the PI3K and MAPK pathways as well as PI3K-independent mTOR activity, which result in differential phosphorylation of specific rpS6 serine residues. These results place rpS6 phosphorylation as a point of convergence for multiple crucial signaling pathways downstream of TCR triggering.
Heather S. Kain - One of the best experts on this subject based on the ideXlab platform.
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alterations in phosphorylation of hepatocyte Ribosomal Protein S6 control plasmodium liver stage infection
Cell Reports, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan VijayanAbstract:Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.
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Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection
Elsevier, 2019Co-Authors: Elizabeth K.k. Glennon, Laura S. Austin, Nadia Arang, Heather S. Kain, Fred D. Mast, Kamalakannan Vijayan, John D. Aitchison, Stefan H.i. Kappe, Alexis KaushanskyAbstract:Summary: Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated Ribosomal Protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection. : After mosquito-to-human transmission, Plasmodium parasites infect hepatocytes. Glennon et al. demonstrate that infected cells exhibit elevated levels of Ribosomal Protein S6 phosphorylation, and this phosphorylation appears uncoupled from canonical regulators. This work raises the possibility that Plasmodium-infected hepatocytes are governed by non-canonical, re-wired signal transduction cascades. Keywords: hepatocyte, Plasmodium, Ribosomal Protein S6, Toxoplasma, signal transductio
