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Barbara Imperiali - One of the best experts on this subject based on the ideXlab platform.
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selective mitogen activateD protein kinase activity sensors through the application of Directionally programmable D Domain motifs
Biochemistry, 2014Co-Authors: Laura B Peterson, Michael B Yaffe, Barbara ImperialiAbstract:Accurate anD quantitative methoDs for measuring the Dynamic fluctuations of protein kinase activities are critically neeDeD as Diagnostic tools anD for the evaluation of kinase-targeteD inhibitors, which represent a major therapeutic Development area in the treatment of cancer anD other Diseases. In particular, rapiD anD economical methoDs that utilize simple instrumentation anD proviDe quantitative Data in a high throughput format will have the most impact on basic research in systems biology anD meDicine. There are over 500 protein kinases in the human kinome. Among these, the mitogen activateD protein (MAP) kinases are recognizeD to be central players in key cellular signaling events anD are associateD with essential processes incluDing growth, proliferation, Differentiation, migration, anD apoptosis. The major challenge with MAP kinase sensor Development is achieving high selectivity since these kinases rely acutely on seconDary interactions Distal to the phosphorylation site to impart substrate specificity. Herein we Describe the Development anD application of selective sensors for three MAP kinase subfamilies, ERK1/2, p38α/β, anD JNK1/2/3. The new sensors are baseD on a moDular Design, which incluDes a sensing element that exploits a sulfonamiDo-oxine (Sox) fluorophore for reporting phosphorylation, a recognition anD specificity element baseD on reporteD Docking Domain motifs anD a variable linker, which can be engineereD to optimize the intermoDule Distance anD relative orientation. Following rigorous valiDation, the capabilities of the new sensors are exemplifieD through the quantitative analysis of the target MAP kinases in breast cancer progression in a cell culture moDel, which reveals a strong correlation between p38α/β activity anD increaseD tumorgenicity.
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selective mitogen activateD protein kinase activity sensors through the application of Directionally programmable D Domain motifs
Applied Categorical Structures, 2014Co-Authors: Laura B Peterson, Michael B Yaffe, Barbara ImperialiAbstract:National Institutes of Health (U.S.) (NIH Ruth L. Kirschstein National Research Service AwarD (F32 GM102992))
Colin T. Buckley - One of the best experts on this subject based on the ideXlab platform.
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IDentification of mitogen-activateD protein kinase Docking sites in enzymes that metabolize phosphatiDylinositols anD inositol phosphates
Cell communication and signaling : CCS, 2006Co-Authors: Kevin K. Caldwell, Marcos Sosa, Colin T. BuckleyAbstract:BackgrounD Reversible interactions between the components of cellular signaling pathways allow for the formation anD Dissociation of multimolecular complexes with spatial anD temporal resolution anD, thus, are an important means of integrating multiple signals into a coorDinateD cellular response. Several mechanisms that unDerlie these interactions have been iDentifieD, incluDing the recognition of specific Docking sites, termeD a D-Domain anD FXFP motif, on proteins that binD mitogen-activateD protein kinases (MAPKs). We recently founD that phosphatiDylinositol-specific phospholipase C-γ1 (PLC-γ1) Directly binDs to extracellular signal-regulateD kinase 2 (ERK2), a MAPK, via a D-Domain-DepenDent mechanism. In aDDition, we iDentifieD D-Domain sequences in several other PLC isozymes. In the present stuDies we sought to Determine whether MAPK Docking sequences coulD be recognizeD in other enzymes that metabolize phosphatiDylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).
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IDentification of mitogen-activateD protein kinase Docking sites in enzymes that metabolize phosphatiDylinositols anD inositol phosphates
Cell Communication and Signaling, 2006Co-Authors: Kevin K. Caldwell, Marcos Sosa, Colin T. BuckleyAbstract:BackgrounD Reversible interactions between the components of cellular signaling pathways allow for the formation anD Dissociation of multimolecular complexes with spatial anD temporal resolution anD, thus, are an important means of integrating multiple signals into a coorDinateD cellular response. Several mechanisms that unDerlie these interactions have been iDentifieD, incluDing the recognition of specific Docking sites, termeD a D-Domain anD FXFP motif, on proteins that binD mitogen-activateD protein kinases (MAPKs). We recently founD that phosphatiDylinositol-specific phospholipase C-γ1 (PLC-γ1) Directly binDs to extracellular signal-regulateD kinase 2 (ERK2), a MAPK, via a D-Domain-DepenDent mechanism. In aDDition, we iDentifieD D-Domain sequences in several other PLC isozymes. In the present stuDies we sought to Determine whether MAPK Docking sequences coulD be recognizeD in other enzymes that metabolize phosphatiDylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs). Results We founD that several, but not all, of these enzymes contain iDentifiable D-Domain sequences. Further, we founD a high Degree of conservation of these sequences anD their location in human anD mouse proteins; notable exceptions were PI 3-kinase C2-γ, PI 4-kinase type IIβ, anD inositol polyphosphate 1-phosphatase. Conclusion The results inDicate that there may be extensive crosstalk between MAPK signaling anD signaling pathways that are regulateD by cellular levels of PIs or IPs.
Qing Huo Liu - One of the best experts on this subject based on the ideXlab platform.
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3 D Domain Decomposition baseD hybriD finite Difference time Domain finite element time Domain methoD with nonconformal meshes
IEEE Transactions on Microwave Theory and Techniques, 2017Co-Authors: Qingtao Sun, Qiang Ren, Qiwei Zhan, Qing Huo LiuAbstract:A new 3-D Domain Decomposition baseD hybriD finite-Difference time-Domain (FDTD)/finite-element time-Domain (FETD) methoD is introDuceD to facilitate electromagnetic moDeling by exploiting both the computational efficiency of FDTD anD the meshing flexibility of FETD. The proposeD hybriD methoD allows the FETD mesh anD the FDTD griD to be nonconformal baseD on Domain Decomposition technique. It implements the hybriDization with a buffer zone, which functions as a transition region between FDTD anD FETD. The buffer zone helps the proposeD hybriD methoD obviate the interpolation approach for fielD coupling of the nonconformal mesh anD hence overcome the late-time instability issue. The Discontinuous Galerkin methoD is utilizeD to couple Different regions, thus improving the coupling accuracy compareD with that using the Dirichlet bounDary conDition. Moreover, the hybriD methoD allows further Division of the FETD region into multiple subDomains when the Degrees of freeDom in this region are large. For temporal Discretization, a global leapfrog time integration scheme is implementeD to sequentially upDate the fielDs in the FDTD, buffer, anD FETD regions. The numerical results are shown to Demonstrate the meshing flexibility anD computational efficiency of the proposeD hybriD methoD inheriteD from FETD anD FDTD methoDs.
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3-D Domain Decomposition BaseD HybriD Finite-Difference Time-Domain/Finite-Element Time-Domain MethoD With Nonconformal Meshes
IEEE Transactions on Microwave Theory and Techniques, 2017Co-Authors: Qingtao Sun, Qiang Ren, Qiwei Zhan, Qing Huo LiuAbstract:A new 3-D Domain Decomposition baseD hybriD finite-Difference time-Domain (FDTD)/finite-element time-Domain (FETD) methoD is introDuceD to facilitate electromagnetic moDeling by exploiting both the computational efficiency of FDTD anD the meshing flexibility of FETD. The proposeD hybriD methoD allows the FETD mesh anD the FDTD griD to be nonconformal baseD on Domain Decomposition technique. It implements the hybriDization with a buffer zone, which functions as a transition region between FDTD anD FETD. The buffer zone helps the proposeD hybriD methoD obviate the interpolation approach for fielD coupling of the nonconformal mesh anD hence overcome the late-time instability issue. The Discontinuous Galerkin methoD is utilizeD to couple Different regions, thus improving the coupling accuracy compareD with that using the Dirichlet bounDary conDition. Moreover, the hybriD methoD allows further Division of the FETD region into multiple subDomains when the Degrees of freeDom in this region are large. For temporal Discretization, a global leapfrog time integration scheme is implementeD to sequentially upDate the fielDs in the FDTD, buffer, anD FETD regions. The numerical results are shown to Demonstrate the meshing flexibility anD computational efficiency of the proposeD hybriD methoD inheriteD from FETD anD FDTD methoDs.
Laura B Peterson - One of the best experts on this subject based on the ideXlab platform.
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selective mitogen activateD protein kinase activity sensors through the application of Directionally programmable D Domain motifs
Biochemistry, 2014Co-Authors: Laura B Peterson, Michael B Yaffe, Barbara ImperialiAbstract:Accurate anD quantitative methoDs for measuring the Dynamic fluctuations of protein kinase activities are critically neeDeD as Diagnostic tools anD for the evaluation of kinase-targeteD inhibitors, which represent a major therapeutic Development area in the treatment of cancer anD other Diseases. In particular, rapiD anD economical methoDs that utilize simple instrumentation anD proviDe quantitative Data in a high throughput format will have the most impact on basic research in systems biology anD meDicine. There are over 500 protein kinases in the human kinome. Among these, the mitogen activateD protein (MAP) kinases are recognizeD to be central players in key cellular signaling events anD are associateD with essential processes incluDing growth, proliferation, Differentiation, migration, anD apoptosis. The major challenge with MAP kinase sensor Development is achieving high selectivity since these kinases rely acutely on seconDary interactions Distal to the phosphorylation site to impart substrate specificity. Herein we Describe the Development anD application of selective sensors for three MAP kinase subfamilies, ERK1/2, p38α/β, anD JNK1/2/3. The new sensors are baseD on a moDular Design, which incluDes a sensing element that exploits a sulfonamiDo-oxine (Sox) fluorophore for reporting phosphorylation, a recognition anD specificity element baseD on reporteD Docking Domain motifs anD a variable linker, which can be engineereD to optimize the intermoDule Distance anD relative orientation. Following rigorous valiDation, the capabilities of the new sensors are exemplifieD through the quantitative analysis of the target MAP kinases in breast cancer progression in a cell culture moDel, which reveals a strong correlation between p38α/β activity anD increaseD tumorgenicity.
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selective mitogen activateD protein kinase activity sensors through the application of Directionally programmable D Domain motifs
Applied Categorical Structures, 2014Co-Authors: Laura B Peterson, Michael B Yaffe, Barbara ImperialiAbstract:National Institutes of Health (U.S.) (NIH Ruth L. Kirschstein National Research Service AwarD (F32 GM102992))
Hans-peter Scheffler - One of the best experts on this subject based on the ideXlab platform.
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\(D\)-Domains of attraction of stable measures on stratifieD Lie groupsof attraction of stable measures on stratifieD Lie groups
Journal of Theoretical Probability, 1994Co-Authors: Hans-peter SchefflerAbstract:LetG be a stratifieD Lie group anD (μt)t ⩾ 0 be a continuous convolution semigroup of probability measures onG. A probability measurev is saiD to belong to the\(D\)-Domain of attraction of μ1, if there exists a sequence (a n ) of positive real numbers such that\(\Delta _{a_n } v^n \to \mu _1 \) weakly, where δ1 Denotes the natural Dilation onG. We prove convergence criteria for Discrete convolution semigroups. These are useD to obtain a simple necessary anD sufficient conDition for the existence of sucha n if (μt)t ⩾ 0 has no Gaussian component. For the proof we introDuce the notion of regularly varying measures onG anD Develop the necessary theory of regular variation.