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Robert E. Lewis - One of the best experts on this subject based on the ideXlab platform.
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Coordinating ERK signaling via the Molecular Scaffold Kinase Suppressor of Ras
F1000Research, 2017Co-Authors: Danielle Frodyma, Diane L. Costanzo-garvey, Beth K. Neilsen, Kurt W. Fisher, Robert E. LewisAbstract:Many cancers, including those of the colon, lung, and pancreas, depend upon the signaling pathways induced by mutated and constitutively active Ras. The Molecular Scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade. Here we summarize the canonical role of KSR in cells, including its central role as a Scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of various cellular pathways mediated through different binding partners, and the phenotypic consequences of KSR1 or KSR2 genetic inactivation. Mammalian KSR proteins have a demonstrated role in cellular and organismal energy balance with implications for cancer and obesity. Targeting KSR1 in cancer using small molecule inhibitors has potential for therapy with reduced toxicity to the patient. RNAi and small molecule screens using KSR1 as a reference standard have the potential to expose and target vulnerabilities in cancer. Interestingly, although KSR1 and KSR2 are similar in structure, KSR2 has a distinct physiological role in regulating energy balance. Although KSR proteins have been studied for two decades, additional analysis is required to elucidate both the regulation of these Molecular Scaffolds and their potent effect on the spatial and temporal control of ERK activation in health and disease.
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Regulation of glucose homeostasis by KSR1 and MARK2
PloS one, 2011Co-Authors: Paula J. Klutho, Diane L. Costanzo-garvey, Robert E. LewisAbstract:Protein Scaffolds control the intensity and duration of signaling and dictate the specificity of signaling through MAP kinase pathways. KSR1 is a Molecular Scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. Relative to wild-type mice, ksr1-/- mice are modestly glucose intolerant, but show a normal response to exogenous insulin. However, ksr1-/- mice also demonstrate a three-fold increase in serum insulin levels in response to a glucose challenge, suggesting a role for KSR1 in insulin secretion. The kinase MARK2 is closely related to C-TAK1, a known regulator of KSR1. Mice lacking MARK2 have an increased rate of glucose disposal in response to exogenous insulin, increased glucose tolerance, and are resistant to diet-induced obesity. mark2-/-ksr1-/- (DKO) mice were compared to wild type, mark2-/-, and ksr1-/- mice for their ability to regulate glucose homeostasis. Here we show that disruption of KSR1 in mark2-/- mice reverses the increased sensitivity to exogenous insulin resulting from MARK2 deletion. DKO mice respond to exogenous insulin similarly to wild type and ksr1-/- mice. These data suggest a model whereby MARK2 negatively regulates insulin sensitivity in peripheral tissue through inhibition of KSR1. Consistent with this model, we found that MARK2 binds and phosphorylates KSR1 on Ser392. Phosphorylation of Ser392 is a critical regulator of KSR1 stability, subcellular location, and ERK activation. These data reveal an unexpected role for the Molecular Scaffold KSR1 in insulin-regulated glucose metabolism.
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ksr1 is required for cell cycle reinitiation following dna damage
Journal of Biological Chemistry, 2009Co-Authors: Gina L. Razidlo, Heidi J. Johnson, Scott M Stoeger, Kenneth H Cowan, Tadayoshi Bessho, Robert E. LewisAbstract:KSR1 (kinase suppressor of Ras 1) is a Molecular Scaffold and positive regulator of the Raf/MEK/ERK phosphorylation cascade. KSR1 is required for maximal ERK activation induced by growth factors and by some cytotoxic agents. We show here that KSR1 is also required for maximal ERK activation induced by UV light, ionizing radiation, or the DNA interstrand cross-linking agent mitomycin C (MMC). We further demonstrate a role for KSR1 in the reinitiation of the cell cycle and proliferation following cell cycle arrest induced by MMC. Cells lacking KSR1 underwent but did not recover from MMC-induced G2/M arrest. Expression of KSR1 allowed KSR1–/– cells to re-enter the cell cycle following MMC treatment. However, cells expressing a mutated form of KSR1 unable to bind ERK did not recover from MMC-induced cell cycle arrest, demonstrating the requirement for the KSR1-ERK interaction. In addition, constitutive activation of ERK was not sufficient to promote cell cycle reinitiation in MMC-treated KSR1–/– cells. Only cells expressing KSR1 recovered from MMC-induced cell cycle arrest. Importantly, MMC-induced DNA damage was repaired in KSR1–/– cells, as determined by resolution of γ-H2AX-containing foci. These data indicate that cell cycle reinitiation is not actively signaled in the absence of KSR1, even when DNA damage has been resolved. These data reveal a specific role for the Molecular Scaffold KSR1 and KSR1-mediated ERK signaling in the cellular response to DNA interstrand cross-links.
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The Molecular Scaffold kinase suppressor of Ras 1 is a modifier of RasV12-induced and replicative senescence.
Molecular and cellular biology, 2006Co-Authors: Robert L. Kortum, Diane L. Costanzo, Gina L. Razidlo, Deanna J. Volle, Heidi J. Johnson, Angela M. Fusello, Andrey S. Shaw, Robert E. LewisAbstract:In primary mouse embryo fibroblasts (MEFs), oncogenic Ras induces growth arrest via Raf/MEK/extracellular signal-regulated kinase (ERK)-mediated activation of the p19ARF/p53 and INK4/Rb tumor suppressor pathways. Ablation of these same pathways causes spontaneous immortalization in MEFs, and oncogenic transformation by Ras requires ablation of one or both of these pathways. We show that Kinase Suppressor of Ras 1 (KSR1), a Molecular Scaffold for the Raf/MEK/ERK cascade, is necessary for RasV12-induced senescence, and its disruption enhances primary MEF immortalization. RasV12 failed to induce p53, p19ARF, p16INK4a, and p15INK4b expression in KSR1−/− MEFs and increased proliferation instead of causing growth arrest. Reintroduction of wild-type KSR1, but not a mutated KSR1 construct unable to bind activated ERK, rescued RasV12-induced senescence. On continuous culture, deletion of KSR1 accelerated the establishment of spontaneously immortalized cultures and increased the proportion of cultures escaping replicative crisis. Despite enhancing escape from both RasV12-induced and replicative senescence, however, both primary and immortalized KSR1−/− MEFs are completely resistant to RasV12-induced transformation. These data show that escape from senescence is not necessarily a precursor for oncogenic transformation. Furthermore, these data indicate that KSR1 is a member of a unique class of proteins whose deletion blocks both senescence and transformation.
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The Molecular Scaffold KSR1 Regulates the Proliferative and Oncogenic Potential of Cells
Molecular and cellular biology, 2004Co-Authors: Robert L. Kortum, Robert E. LewisAbstract:Mitogen-activated protein (MAP) kinase pathways are implicated in the control of multiple aspects of cell fate, including senescence, proliferation, transformation, differentiation, and apoptosis (7, 30, 34, 47). While the components of these ubiquitous pathways are well established, the means by which they direct cell fate remain unclear. Recently, two ideas for the control of signal outputs from MAP kinase pathways have emerged: the duration and intensity of MAP kinase activation can dictate which targets become phosphorylated (27) and Scaffold proteins organize specific MAP kinase cascades to ensure signal specificity (5, 34, 47). The intensity and duration of ERK activation are critical determinants of ERK's ability to modulate a diverse array of cellular processes (16, 22, 27, 30, 32). In PC12 cells, epidermal growth factor (EGF) induces a transient activation of ERK in the cytoplasm, leading to proliferation. Conversely, nerve growth factor (NGF) induces both a prolonged activation of ERK and the translocation of ERK to the nucleus, leading to differentiation into neurons (22). In mammalian fibroblasts, treatment with EGF induces a transient activation of ERK, whereas treatment with platelet-derived growth factor (PDGF) causes a sustained activation of ERK. This sustained activation leads to phosphorylation of the immediate-early protein c-Fos and to cell cycle progression (16, 27). Scaffold proteins organize signaling components to determine specificity within MAP kinase cascades (34, 47). Protein Scaffolds of kinase cascades can have varied effects on signaling through their pathways. The prototypic MAP kinase Scaffold Ste5 is essential for the mating pheromone pathway of budding yeast (11). InaD, a Scaffold for Drosophila photoreceptor signaling, is not required, but it greatly enhances the amplitude and kinetics of signaling in this pathway (35). For mammalian cells, several putative Scaffolds for MAP kinase cascades have been identified, including JIP-1 and JIP-2 (10, 46, 50), MP1 (33), and KSR1 (24, 28, 41). While each Scaffold has been proposed to enhance signaling through the c-Jun N-terminal kinase, ERK1, or ERK1/2 pathway, respectively, each has been shown to inhibit signaling when it is overexpressed (8, 10, 16, 33, 52). The biological consequences of overexpression of these proteins are consistent with their proposed role as Scaffold proteins, since Molecular Scaffolds of kinase cascades are predicted to affect signal output in a concentration-dependent manner, facilitating signaling to an optimal concentration and inhibiting signaling beyond this optimum (5, 12, 15, 20). KSR1 is a Scaffold for the Raf/MEK/ERK kinase cascade (24, 28, 31) and has been proposed to act in such a manner, as low levels of expression lead to increased pathway activity (2, 6, 23, 25, 28, 29, 41, 48) and high levels of expression inhibit signaling through the pathway (4, 6, 8, 17, 37, 52). Here we examine the role of the Molecular Scaffold KSR1 in facilitating the intensity and duration of ERK activation to affect cell proliferation and oncogenic transformation. We show that the loss of KSR1 reduces growth factor-induced ERK activation and that the reintroduction of KSR1 into KSR1−/− mouse embryo fibroblasts (MEFs) rescues this deficit in a dose-dependent manner. Furthermore, KSR1 is necessary and sufficient for RasV12-induced transformation, with a dose dependence similar to that seen for signaling. When KSR1 levels are optimized, the cellular response to EGF is converted to a PDGF-like response, including the promotion of prolonged ERK activation and the exit of quiescent cells from G0 into S phase. Optimal levels of KSR1 expression also lead to a threefold increase in the proliferative capacity. These data indicate that altering the expression level of a Molecular Scaffold can modulate the actions of growth factors and oncogenes.
Hilda A Pickett - One of the best experts on this subject based on the ideXlab platform.
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NuRD–ZNF827 recruitment to telomeres creates a Molecular Scaffold for homologous recombination
Nature Structural & Molecular Biology, 2014Co-Authors: Dimitri Conomos, Roger R Reddel, Hilda A PickettAbstract:Alternative lengthening of telomeres (ALT) is a homologous recombination (HR)-dependent mechanism for de novo synthesis of telomeric DNA in mammalian cells. Nuclear receptors are bound to the telomeres of cells that use ALT. Here we demonstrate that nuclear receptors recruit ZNF827, a zinc-finger protein of unknown function, which recruits the nucleosome remodeling and histone deacetylation (NuRD) complex via binding to an N-terminal RRK motif within ZNF827. This results in decreased shelterin binding, hypoacetylation of telomeric chromatin, enhanced telomere-telomere interactions and recruitment of HR proteins, and it is critically important for cell viability and proliferation. We propose that NuRD–ZNF827 recruitment to human telomeres causes remodeling of telomeric chromatin and creates an environment that promotes telomere-telomere recombination and integrates and controls multiple mechanistic elements of ALT activity. Cancer cells lacking telomerase maintain telomere lengths required for cell growth through a recombination mechanism called ALT. Now, ALT-specific nuclear receptors are shown to recruit a zinc-finger protein that directs the nucleosome remodeler and histone deacetylase NuRD to telomeres to enhance homologous recombination.
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nurd znf827 recruitment to telomeres creates a Molecular Scaffold for homologous recombination
Nature Structural & Molecular Biology, 2014Co-Authors: Dimitri Conomos, Roger R Reddel, Hilda A PickettAbstract:Cancer cells lacking telomerase maintain telomere lengths required for cell growth through a recombination mechanism called ALT. Now, ALT-specific nuclear receptors are shown to recruit a zinc-finger protein that directs the nucleosome remodeler and histone deacetylase NuRD to telomeres to enhance homologous recombination.
Robert L. Kortum - One of the best experts on this subject based on the ideXlab platform.
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The Molecular Scaffold kinase suppressor of Ras 1 is a modifier of RasV12-induced and replicative senescence.
Molecular and cellular biology, 2006Co-Authors: Robert L. Kortum, Diane L. Costanzo, Gina L. Razidlo, Deanna J. Volle, Heidi J. Johnson, Angela M. Fusello, Andrey S. Shaw, Robert E. LewisAbstract:In primary mouse embryo fibroblasts (MEFs), oncogenic Ras induces growth arrest via Raf/MEK/extracellular signal-regulated kinase (ERK)-mediated activation of the p19ARF/p53 and INK4/Rb tumor suppressor pathways. Ablation of these same pathways causes spontaneous immortalization in MEFs, and oncogenic transformation by Ras requires ablation of one or both of these pathways. We show that Kinase Suppressor of Ras 1 (KSR1), a Molecular Scaffold for the Raf/MEK/ERK cascade, is necessary for RasV12-induced senescence, and its disruption enhances primary MEF immortalization. RasV12 failed to induce p53, p19ARF, p16INK4a, and p15INK4b expression in KSR1−/− MEFs and increased proliferation instead of causing growth arrest. Reintroduction of wild-type KSR1, but not a mutated KSR1 construct unable to bind activated ERK, rescued RasV12-induced senescence. On continuous culture, deletion of KSR1 accelerated the establishment of spontaneously immortalized cultures and increased the proportion of cultures escaping replicative crisis. Despite enhancing escape from both RasV12-induced and replicative senescence, however, both primary and immortalized KSR1−/− MEFs are completely resistant to RasV12-induced transformation. These data show that escape from senescence is not necessarily a precursor for oncogenic transformation. Furthermore, these data indicate that KSR1 is a member of a unique class of proteins whose deletion blocks both senescence and transformation.
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The Molecular Scaffold Kinase Suppressor of Ras 1 (KSR1) Regulates Adipogenesis
Molecular and cellular biology, 2005Co-Authors: Robert L. Kortum, Diane L. Costanzo, Jamie L. Haferbier, Steven J. Schreiner, Gina L. Razidlo, Deanna J. Volle, Toshiyuki Mori, Hiroshi Sakaue, Nina V. ChaikaAbstract:Mitogen-activated protein kinase pathways are implicated in the regulation of cell differentiation, although their precise roles in many differentiation programs remain elusive. The Raf/MEK/extracellular signal-regulated kinase (ERK) kinase cascade has been proposed to both promote and inhibit adipogenesis. Here, we titrate expression of the Molecular Scaffold kinase suppressor of Ras 1 (KSR1) to regulate signaling through the Raf/MEK/ERK/p90 ribosomal S6 kinase (RSK) kinase cascade and show how it determines adipogenic potential. Deletion of KSR1 prevents adipogenesis in vitro, which can be rescued by introduction of low levels of KSR1. Appropriate levels of KSR1 coordinate ERK and RSK activation with C/EBPbeta synthesis leading to the phosphorylation and stabilization of C/EBPbeta at the precise moment it is required within the adipogenic program. Elevated levels of KSR1 expression, previously shown to enhance cell proliferation, promote high, sustained ERK activation that phosphorylates and inhibits peroxisome proliferator-activated receptor gamma, inhibiting adipogenesis. Titration of KSR1 expression reveals how a Molecular Scaffold can modulate the intensity and duration of signaling emanating from a single pathway to dictate cell fate.
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The Molecular Scaffold KSR1 Regulates the Proliferative and Oncogenic Potential of Cells
Molecular and cellular biology, 2004Co-Authors: Robert L. Kortum, Robert E. LewisAbstract:Mitogen-activated protein (MAP) kinase pathways are implicated in the control of multiple aspects of cell fate, including senescence, proliferation, transformation, differentiation, and apoptosis (7, 30, 34, 47). While the components of these ubiquitous pathways are well established, the means by which they direct cell fate remain unclear. Recently, two ideas for the control of signal outputs from MAP kinase pathways have emerged: the duration and intensity of MAP kinase activation can dictate which targets become phosphorylated (27) and Scaffold proteins organize specific MAP kinase cascades to ensure signal specificity (5, 34, 47). The intensity and duration of ERK activation are critical determinants of ERK's ability to modulate a diverse array of cellular processes (16, 22, 27, 30, 32). In PC12 cells, epidermal growth factor (EGF) induces a transient activation of ERK in the cytoplasm, leading to proliferation. Conversely, nerve growth factor (NGF) induces both a prolonged activation of ERK and the translocation of ERK to the nucleus, leading to differentiation into neurons (22). In mammalian fibroblasts, treatment with EGF induces a transient activation of ERK, whereas treatment with platelet-derived growth factor (PDGF) causes a sustained activation of ERK. This sustained activation leads to phosphorylation of the immediate-early protein c-Fos and to cell cycle progression (16, 27). Scaffold proteins organize signaling components to determine specificity within MAP kinase cascades (34, 47). Protein Scaffolds of kinase cascades can have varied effects on signaling through their pathways. The prototypic MAP kinase Scaffold Ste5 is essential for the mating pheromone pathway of budding yeast (11). InaD, a Scaffold for Drosophila photoreceptor signaling, is not required, but it greatly enhances the amplitude and kinetics of signaling in this pathway (35). For mammalian cells, several putative Scaffolds for MAP kinase cascades have been identified, including JIP-1 and JIP-2 (10, 46, 50), MP1 (33), and KSR1 (24, 28, 41). While each Scaffold has been proposed to enhance signaling through the c-Jun N-terminal kinase, ERK1, or ERK1/2 pathway, respectively, each has been shown to inhibit signaling when it is overexpressed (8, 10, 16, 33, 52). The biological consequences of overexpression of these proteins are consistent with their proposed role as Scaffold proteins, since Molecular Scaffolds of kinase cascades are predicted to affect signal output in a concentration-dependent manner, facilitating signaling to an optimal concentration and inhibiting signaling beyond this optimum (5, 12, 15, 20). KSR1 is a Scaffold for the Raf/MEK/ERK kinase cascade (24, 28, 31) and has been proposed to act in such a manner, as low levels of expression lead to increased pathway activity (2, 6, 23, 25, 28, 29, 41, 48) and high levels of expression inhibit signaling through the pathway (4, 6, 8, 17, 37, 52). Here we examine the role of the Molecular Scaffold KSR1 in facilitating the intensity and duration of ERK activation to affect cell proliferation and oncogenic transformation. We show that the loss of KSR1 reduces growth factor-induced ERK activation and that the reintroduction of KSR1 into KSR1−/− mouse embryo fibroblasts (MEFs) rescues this deficit in a dose-dependent manner. Furthermore, KSR1 is necessary and sufficient for RasV12-induced transformation, with a dose dependence similar to that seen for signaling. When KSR1 levels are optimized, the cellular response to EGF is converted to a PDGF-like response, including the promotion of prolonged ERK activation and the exit of quiescent cells from G0 into S phase. Optimal levels of KSR1 expression also lead to a threefold increase in the proliferative capacity. These data indicate that altering the expression level of a Molecular Scaffold can modulate the actions of growth factors and oncogenes.
Gina L. Razidlo - One of the best experts on this subject based on the ideXlab platform.
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ksr1 is required for cell cycle reinitiation following dna damage
Journal of Biological Chemistry, 2009Co-Authors: Gina L. Razidlo, Heidi J. Johnson, Scott M Stoeger, Kenneth H Cowan, Tadayoshi Bessho, Robert E. LewisAbstract:KSR1 (kinase suppressor of Ras 1) is a Molecular Scaffold and positive regulator of the Raf/MEK/ERK phosphorylation cascade. KSR1 is required for maximal ERK activation induced by growth factors and by some cytotoxic agents. We show here that KSR1 is also required for maximal ERK activation induced by UV light, ionizing radiation, or the DNA interstrand cross-linking agent mitomycin C (MMC). We further demonstrate a role for KSR1 in the reinitiation of the cell cycle and proliferation following cell cycle arrest induced by MMC. Cells lacking KSR1 underwent but did not recover from MMC-induced G2/M arrest. Expression of KSR1 allowed KSR1–/– cells to re-enter the cell cycle following MMC treatment. However, cells expressing a mutated form of KSR1 unable to bind ERK did not recover from MMC-induced cell cycle arrest, demonstrating the requirement for the KSR1-ERK interaction. In addition, constitutive activation of ERK was not sufficient to promote cell cycle reinitiation in MMC-treated KSR1–/– cells. Only cells expressing KSR1 recovered from MMC-induced cell cycle arrest. Importantly, MMC-induced DNA damage was repaired in KSR1–/– cells, as determined by resolution of γ-H2AX-containing foci. These data indicate that cell cycle reinitiation is not actively signaled in the absence of KSR1, even when DNA damage has been resolved. These data reveal a specific role for the Molecular Scaffold KSR1 and KSR1-mediated ERK signaling in the cellular response to DNA interstrand cross-links.
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The Molecular Scaffold kinase suppressor of Ras 1 is a modifier of RasV12-induced and replicative senescence.
Molecular and cellular biology, 2006Co-Authors: Robert L. Kortum, Diane L. Costanzo, Gina L. Razidlo, Deanna J. Volle, Heidi J. Johnson, Angela M. Fusello, Andrey S. Shaw, Robert E. LewisAbstract:In primary mouse embryo fibroblasts (MEFs), oncogenic Ras induces growth arrest via Raf/MEK/extracellular signal-regulated kinase (ERK)-mediated activation of the p19ARF/p53 and INK4/Rb tumor suppressor pathways. Ablation of these same pathways causes spontaneous immortalization in MEFs, and oncogenic transformation by Ras requires ablation of one or both of these pathways. We show that Kinase Suppressor of Ras 1 (KSR1), a Molecular Scaffold for the Raf/MEK/ERK cascade, is necessary for RasV12-induced senescence, and its disruption enhances primary MEF immortalization. RasV12 failed to induce p53, p19ARF, p16INK4a, and p15INK4b expression in KSR1−/− MEFs and increased proliferation instead of causing growth arrest. Reintroduction of wild-type KSR1, but not a mutated KSR1 construct unable to bind activated ERK, rescued RasV12-induced senescence. On continuous culture, deletion of KSR1 accelerated the establishment of spontaneously immortalized cultures and increased the proportion of cultures escaping replicative crisis. Despite enhancing escape from both RasV12-induced and replicative senescence, however, both primary and immortalized KSR1−/− MEFs are completely resistant to RasV12-induced transformation. These data show that escape from senescence is not necessarily a precursor for oncogenic transformation. Furthermore, these data indicate that KSR1 is a member of a unique class of proteins whose deletion blocks both senescence and transformation.
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The Molecular Scaffold Kinase Suppressor of Ras 1 (KSR1) Regulates Adipogenesis
Molecular and cellular biology, 2005Co-Authors: Robert L. Kortum, Diane L. Costanzo, Jamie L. Haferbier, Steven J. Schreiner, Gina L. Razidlo, Deanna J. Volle, Toshiyuki Mori, Hiroshi Sakaue, Nina V. ChaikaAbstract:Mitogen-activated protein kinase pathways are implicated in the regulation of cell differentiation, although their precise roles in many differentiation programs remain elusive. The Raf/MEK/extracellular signal-regulated kinase (ERK) kinase cascade has been proposed to both promote and inhibit adipogenesis. Here, we titrate expression of the Molecular Scaffold kinase suppressor of Ras 1 (KSR1) to regulate signaling through the Raf/MEK/ERK/p90 ribosomal S6 kinase (RSK) kinase cascade and show how it determines adipogenic potential. Deletion of KSR1 prevents adipogenesis in vitro, which can be rescued by introduction of low levels of KSR1. Appropriate levels of KSR1 coordinate ERK and RSK activation with C/EBPbeta synthesis leading to the phosphorylation and stabilization of C/EBPbeta at the precise moment it is required within the adipogenic program. Elevated levels of KSR1 expression, previously shown to enhance cell proliferation, promote high, sustained ERK activation that phosphorylates and inhibits peroxisome proliferator-activated receptor gamma, inhibiting adipogenesis. Titration of KSR1 expression reveals how a Molecular Scaffold can modulate the intensity and duration of signaling emanating from a single pathway to dictate cell fate.
Jongmin Kang - One of the best experts on this subject based on the ideXlab platform.
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A new anion receptor with biquinoline Molecular Scaffold
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2012Co-Authors: Young-hee Kim, Jongmin Kang, Jiwon Moon, Seung Joo ChoAbstract:We have designed and synthesized a new fluorescent receptor 3 utilizing biquinoline as a Molecular Scaffold. The receptor 3 has two amide hydrogens and two carbamate hydrogens anchored at 4,4′-position of biquinoline. Fluorescence and 1H NMR titration showed that receptor 3 bound anions with different stoichiometry depending on the shape of anions and its association constants for anions reflected the basicities of anions. Receptor 3 bound chloride, acetate and benzoate in 1:2 stoichiometry and had a highest affinity for acetate. Tetrahedral shaped dihydrogen phosphate bound receptor 3 in 1:1 stoichiometry, although its affinity was low.
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Anion receptors with viologen Molecular Scaffold
Tetrahedron Letters, 2012Co-Authors: Jin Joo Park, Young-hee Kim, Sol Rhim, Jongmin KangAbstract:Abstract We have designed and synthesized new anion receptors 1 2+ and 2 2+ . These receptors interact with anions through hydrogen bonds and charge transfer complex depending on the basicity of anion. Therefore, anions with weak basicity such as chloride, bromide, and hydrogen sulfate bound to the receptors 1 2+ and 2 2+ only through hydrogen bonds while anions with strong basicity such as fluoride, acetate and dihydrogen phosphate bound to the receptors 1 2+ and 2 2+ only through charge transfer interactions at UV–vis titration condition (20 μM). However, in more concentrated 1 H NMR titration condition (2 mM), 1 2+ and 2 2+ decomposed to form the product one of their amide arm is eliminated. As charge transfer complexes showed colorimetric response, they turned out to be efficient naked eye detector for anions with strong basicity such as fluoride, acetate, and dihydrogen phosphate.
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Anion Receptors with 2-Imidazolidone Molecular Scaffold
Bulletin of the Korean Chemical Society, 2007Co-Authors: Hyungil Kim, Jongmin KangAbstract:Manyanions have diverse geometries that require shape-selectiverecognition. Therefore, many researchers have used hydro-gen bonds as a recognition element as they are directional.The correct orientation of hydrogen bonds can differentiatebetween anionic guests with different geometries.In nature, the hydrogen bonds are most often utilized toachieve anion binding by proteins.
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anion receptors with glycoluril Molecular Scaffold
Supramolecular Chemistry, 2007Co-Authors: Jongmin Kang, Seung Joo ChoAbstract:For a synthetic receptor with an amide group, the amide groups are arranged through a space in a rigid and convergent manner. This has been achieved by incorporating amide groups into various Molecular Scaffolds. The geometry of diphenylglycoluril allows the synthesis of concave Molecular structures. In addition, the rigidity of the molecule provides a solid Molecular Scaffold to arrange suitable binding moieties such as hydrogen bonds. We have developed various anion receptors based on diphenylglycoluril. The association of these receptors with various anions reflects the shape, size and basicity of the anions.
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Bromide selective fluorescent anion receptor with glycoluril Molecular Scaffold
Tetrahedron Letters, 2005Co-Authors: Jongmin Kang, Jihae KimAbstract:Glycoluril based fluorescent anion receptor has been designed and synthesized. Anion binding studies carried out using fluorescence spectroscopy and 1H NMR revealed that this compound displays good affinities for bromide ion.
