The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Cesare Montecucco - One of the best experts on this subject based on the ideXlab platform.
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anthrax lethal factor cleaves mkk3 in macrophages and inhibits the lps ifnγ induced release of no and tnfα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Chantal Guidirontani, Gaetano Vitale, Michele Mock, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ-induced release of NO and TNFα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha.
FEBS letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated protein Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-alpha induced by lipopolysaccharide/interferon gamma. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
Rossella Pellizzari - One of the best experts on this subject based on the ideXlab platform.
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anthrax lethal factor cleaves mkk3 in macrophages and inhibits the lps ifnγ induced release of no and tnfα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Chantal Guidirontani, Gaetano Vitale, Michele Mock, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ-induced release of NO and TNFα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha.
FEBS letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated protein Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-alpha induced by lipopolysaccharide/interferon gamma. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
Ram Rajasekharan - One of the best experts on this subject based on the ideXlab platform.
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Serine/Threonine/Tyrosine Protein Kinase Phosphorylates Oleosin, a Regulator of Lipid Metabolic Functions
Plant Physiology, 2012Co-Authors: Velayoudame Parthibane, Ramachandiran Iyappan, Anitha Vijayakumar, Varadarajan Venkateshwari, Ram RajasekharanAbstract:Plant oils are stored in oleosomes or oil bodies, which are surrounded by a monolayer of phospholipids embedded with oleosin proteins that stabilize the structure. Recently, a structural protein, Oleosin3 (OLE3), was shown to exhibit both monoacylglycerol acyltransferase and phospholipase A2 activities. The regulation of these distinct dual activities in a single protein is unclear. Here, we report that a serine/threonine/tyrosine protein Kinase phosphorylates oleosin. Using bimolecular fluorescence complementation analysis, we demonstrate that this Kinase interacts with OLE3 and that the fluorescence was associated with chloroplasts. Oleosin-green fluorescent protein fusion protein was exclusively associated with the chloroplasts. Phosphorylated OLE3 exhibited reduced monoacylglycerol acyltransferase and increased phospholipase A2 activities. Moreover, phosphatidylcholine and diacylglycerol activated oleosin phosphorylation, whereas lysophosphatidylcholine, oleic acid, and Ca2+ inhibited phosphorylation. In addition, recombinant peanut (Arachis hypogaea) Kinase was determined to predominantly phosphorylate serine residues, specifically serine-18 in OLE3. Phosphorylation levels of OLE3 during seed germination were determined to be higher than in developing peanut seeds. These findings provide direct evidence for the in vivo substrate selectivity of the Dual-Specificity Kinase and demonstrate that the bifunctional activities of oleosin are regulated by phosphorylation.
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Importance of threonine residues in the regulation of peanut serine/threonine/tyrosine protein Kinase activity
Plant Science, 2007Co-Authors: Mamatha M. Reddy, Parvathi Rudrabhatla, Ram RajasekharanAbstract:Protein tyrosine phosphorylation is carried out by dual- specificity Kinases in plants. Peanut Dual-Specificity Kinase has been shown to be regulated by tyrosine phosphorylation. However, the role of threonine residues in the regulation of peanut serine/threonine/tyrosine (STY) protein Kinase is not yet documented. In the present study, we have investigated the role of threonine residues in the regulation of peanut STY protein Kinase activity. The four threonine residues in the Kinase activation loop and $Thr^{211}$ in the threonine-glutamate-tyrosine (TEY) motif were mutated to alanine to study their role in the regulation of Kinase activity. The protein Kinase activity was abolished when $Thr^{211}$ of TEY motif and $Thr^2^9^6$ of activation loop were converted to alanine, suggesting that they positively regulate the Kinase activity. The ability of T211A and T296A to phosphorylate histone H1 was also reduced drastically. The other mutants T287A, T291A and T294A did not show any change in their ability to autophosphorylate or phosphorylate histone H1 when compared to wild-type peanut STY protein Kinase. Data presented here suggests the importance of threonine residues in the regulation of peanut STY protein Kinase activity and emphasizes the complexity of regulation of dualspecificity protein Kinases in plants.
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Role of threonine residues in the regulation of manganese-dependent arabidopsis serine/threonine/tyrosine protein Kinase activity
Archives of Biochemistry and Biophysics, 2006Co-Authors: Mamatha M. Reddy, Ram RajasekharanAbstract:Tyrosine phosphorylation in plants could be performed only by Dual-Specificity Kinases. Arabidopsis thaliana Dual-Specificity protein Kinase (AtSTYPK) exhibited strong preference for manganese over magnesium for its Kinase activity. The Kinase autophosphorylated on serine, threonine and tyrosine residues and phosphorylated myelin basic protein on threonine and tyrosine residues. The AtSTYPK harbors manganese dependent serine/threonine Kinase domain, COG3642. $His^{248}$ and $Ser^{265}$ on COG3642 are conserved in AtSTYPK and the site-directed mutant, H248A showed loss of serine/threonine Kinase activity. The protein Kinase activity was abolished when $Thr^{208}$ in the TEY motif and $Thr^{293}$ of the activation loop were converted to alanine. The conversion of $Thr^{284}$ in the activation loop to alanine resulted in an increased phosphorylation. This study reports the first identification of a manganese dependent Dual-Specificity Kinase and the importance of $Thr^{208}, Thr^{284}$, and $Thr^{293}$ residues in the regulation of Kinase activity.
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Developmentally Regulated Dual-Specificity Kinase from Peanut That Is Induced by Abiotic Stresses
Plant Physiology, 2002Co-Authors: Parvathi Rudrabhatla, Ram RajasekharanAbstract:Tyrosine (Tyr) phosphorylation represents an important biochemical mechanism to regulate many cellular processes. No Tyr Kinase has been cloned so far in plants. Dual-Specificity Kinases are reported in plants and the function of these Kinases remains unknown. A 1.7-kb cDNA that encodes serine/threonine/Tyr (STY) Kinase was isolated by screening peanut (Arachis hypogaea) expression library using the anti-phospho-Tyr antibody. The histidine-tagged recombinant Kinase histidine-6-STY predominantly autophosphorylated on Tyr and phosphorylated the histone primarily on threonine. Genomic DNA gel-blot analysis revealed that STY Kinase is a member of a small multigene family. The transcript of STY Kinase is accumulated in the mid-maturation stage of seed development, suggesting a role in the signaling of storage of seed reserves. The STY Kinase mRNA expression, as well as Kinase activity, markedly increased in response to cold and salt treatments; however, no change in the protein level was observed, suggesting a posttranslational activation mechanism. The activation of the STY Kinase is detected after 12 to 48 h of cold and salt treatments, which indicates that the Kinase may not participate in the initial response to abiotic stresses, but may play a possible role in the adaptive process to adverse conditions. The transcript levels and Kinase activity were unaltered with abscisic acid treatment, suggesting an abscisic acid-independent cold and salt signaling pathway. Here, we report the first identification of a non-MAP Kinase cascade Dual-Specificity Kinase involved in abiotic stress and seed development.
Gaetano Vitale - One of the best experts on this subject based on the ideXlab platform.
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anthrax lethal factor cleaves mkk3 in macrophages and inhibits the lps ifnγ induced release of no and tnfα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Chantal Guidirontani, Gaetano Vitale, Michele Mock, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ-induced release of NO and TNFα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha.
FEBS letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated protein Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-alpha induced by lipopolysaccharide/interferon gamma. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
Michele Mock - One of the best experts on this subject based on the ideXlab platform.
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anthrax lethal factor cleaves mkk3 in macrophages and inhibits the lps ifnγ induced release of no and tnfα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Chantal Guidirontani, Gaetano Vitale, Michele Mock, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ-induced release of NO and TNFα
FEBS Letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:Abstract The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated proten Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-α induced by lipopolysaccharide/interferonγ. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
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Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha.
FEBS letters, 1999Co-Authors: Rossella Pellizzari, Gaetano Vitale, Michele Mock, Chantal Guidi-rontani, Cesare MontecuccoAbstract:The lethal toxin of Bacillus anthracis consists of two proteins, PA and LF, which together induce lethal effects in animals and cause macrophage lysis. LF is a zinc-endopeptidase which cleaves two mitogen-activated protein Kinase Kinases (MAPKKs), Mek1 and Mek2, within the cytosol. Here, we show that also MKK3, another Dual-Specificity Kinase that phosphorylates and activates p38 MAP Kinase, is cleaved by LF in macrophages. No direct correlation between LF-induced cell death and cleavage of these MAPKKs was found in macrophage cell lines and primary peritoneal cells exhibiting different sensitivity to LF. However, we present the first evidence that sublytic doses of LF cleave Meks and cause a substantial reduction in the production of NO and tumour necrosis factor-alpha induced by lipopolysaccharide/interferon gamma. We suggest that this effect of LF is relevant during the first stages of B. anthracis infection, when a reduction of the inflammatory response would permit growth and diffusion of the bacterium.
