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R V Thampan - One of the best experts on this subject based on the ideXlab platform.
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a 55 kda Protein P55 of the goat uterus mediates nuclear transport of the estrogen receptor ii details of the transport mechanism
Archives of Biochemistry and Biophysics, 1995Co-Authors: P B Nirmala, R V ThampanAbstract:Abstract A 55-kDa Protein (P55) that mediates the transport of the estrogen receptor (ER) from the cytoplasm to the nucleus has been purified to homogeneity from goat uterine cytosol. Using this pure Protein, some of the aspects of the mechanisms associated with the transport of the ER to the nucleus have been elucidated. The mechanism of ER transport into the nucleus can be separated into two steps: the P55-mediated transport and binding of ER to the nuclear membrane, followed by an ATP-dependent, 14-kDa Protein(s)-mediated translocation of ER into the nucleus. The P55 has inherent ATPase activity and it is proposed that the energy released during this ATP hydrolysis is utilized in the nuclear transport of the ER.
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a 55 kda Protein P55 of the goat uterus mediates nuclear transport of the estrogen receptor i purification and characterization
Archives of Biochemistry and Biophysics, 1995Co-Authors: P B Nirmala, R V ThampanAbstract:Abstract A 55-kDa Protein (P55), purified from the goat uterine cytosol, transports estrogen receptor (ER) into the nucleus. Selective elution of this Protein from a column of estrogen receptor-Sepharose using buffers containing high concentrations of lysine and the high affinity with which it binds to poly-L-lysine-Sepharose indicate that it recognizes a lysine-rich region in the ER. Its strong binding to tubulin-Sepharose and actin-Sepharose is indicative of a role that the cytoskeletal elements play in the nuclear transport of the ER, mediated by P55, This Protein can be purified in a single step following chromatography of the uterine cytosol on a column of actin-Sepharose. Antibodies raised against poly-L-aspartic acid cross-reacted with P55 and inhibited the nuclear transport of the ER, The binding of P55 to a heterologous nuclear localization sequence of the SV40 large T suggests that it may also be involved in the transport of Proteins other than the ER.
Athar H Chishti - One of the best experts on this subject based on the ideXlab platform.
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erythrocyte scaffolding Protein P55 mpp1 functions as an essential regulator of neutrophil polarity
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Brendan J Quinn, Emily J Welch, Mary A Lokuta, Anna Huttenlocher, Anwar A Khan, Shafi M Kuchay, Athar H ChishtiAbstract:As mediators of innate immunity, neutrophils respond to chemoattractants by adopting a highly polarized morphology. Efficient chemotaxis requires the formation of one prominent pseudopod at the cell front characterized by actin polymerization, while local inhibition suppresses the formation of rear and lateral protrusions. This asymmetric control of signaling pathways is required for directional migration along a chemotactic gradient. Here, we identify the MAGUK Protein P55/MPP1 as a mediator of the frontness signal required for neutrophil polarization. We developed a P55 knockout (P55−/−) mouse model, and demonstrate that P55−/− neutrophils form multiple transient pseudopods upon chemotactic stimulation, and do not migrate efficiently in vitro. Upon agonist stimulation, P55 is rapidly recruited to the leading edge of neutrophils in mice and humans. Total F-actin polymerization, along with Rac1 and RhoA activation, appear to be normal in P55−/− neutrophils. Importantly, phosphorylation of Akt is significantly decreased in P55−/− neutrophils upon chemotactic stimulation. The activity of immunoprecipitated phosphatidylinositol 3-kinase γ (PI3Kγ), responsible for chemoattractant-induced synthesis of PIP3 and Akt phosphorylation, is unperturbed in P55−/− neutrophils. Although the total amount of PIP3 is normal in P55−/− neutrophils, PIP3 is diffusely localized and forms punctate aggregates in activated P55−/− neutrophils, as compared to its accumulation at the leading edge membrane in the wild type neutrophils. Together, these results show that P55 is required for neutrophil polarization by regulating Akt phosphorylation through a mechanism that is independent of PI3Kγ activity.
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Erythrocyte scaffolding Protein P55/MPP1 functions as an essential regulator of neutrophil polarity
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Brendan J Quinn, Emily J Welch, Mary A Lokuta, Anna Huttenlocher, Anwar A Khan, Shafi M Kuchay, Athar H ChishtiAbstract:As mediators of innate immunity, neutrophils respond to chemoattractants by adopting a highly polarized morphology. Efficient chemotaxis requires the formation of one prominent pseudopod at the cell front characterized by actin polymerization, while local inhibition suppresses the formation of rear and lateral protrusions. This asymmetric control of signaling pathways is required for directional migration along a chemotactic gradient. Here, we identify the MAGUK Protein P55/MPP1 as a mediator of the frontness signal required for neutrophil polarization. We developed a P55 knockout (P55−/−) mouse model, and demonstrate that P55−/− neutrophils form multiple transient pseudopods upon chemotactic stimulation, and do not migrate efficiently in vitro. Upon agonist stimulation, P55 is rapidly recruited to the leading edge of neutrophils in mice and humans. Total F-actin polymerization, along with Rac1 and RhoA activation, appear to be normal in P55−/− neutrophils. Importantly, phosphorylation of Akt is significantly decreased in P55−/− neutrophils upon chemotactic stimulation. The activity of immunoprecipitated phosphatidylinositol 3-kinase γ (PI3Kγ), responsible for chemoattractant-induced synthesis of PIP3 and Akt phosphorylation, is unperturbed in P55−/− neutrophils. Although the total amount of PIP3 is normal in P55−/− neutrophils, PIP3 is diffusely localized and forms punctate aggregates in activated P55−/− neutrophils, as compared to its accumulation at the leading edge membrane in the wild type neutrophils. Together, these results show that P55 is required for neutrophil polarization by regulating Akt phosphorylation through a mechanism that is independent of PI3Kγ activity.
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erythrocyte scaffolding Protein P55 functions as an essential regulator of neutrophil polarity
Blood, 2008Co-Authors: Brendan J Quinn, Athar H ChishtiAbstract:Erythrocyte P55 is a prototypical member of a family of scaffolding Proteins known as Membrane Associated Guanylate Kinase Homologues (MAGUKs). MAGUKs are multi-domain Proteins that couple signals from specialized sites at the plasma membrane to intracellular signal transduction pathways and the cytoskeleton. P55 was originally identified in the erythrocytes as part of a ternary complex with Protein 4.1R and glycophorin C, providing a critical linkage between the actin cytoskeleton and the plasma membrane. Although P55 is expressed in a variety of tissues, especially hematopoietic cells, its biological function is unclear. Here, using a P55 knockout mouse model, we show that P55 plays a prominent role in the regulation of neutrophil polarization. Neutrophils are the first respondents during infection and injury, adopting a highly polarized morphology when stimulated with chemotactic factors. G Proteincoupled surface receptors recognize the external chemotactic gradient and translate it into an internal gradient of signaling molecules. At the front of the cell, accumulation of the lipid product phosphatidylinositol-3,4,5-trisphosphate (PIP3), activation of the small GTPase Rac, and polymerization of F-actin stimulates a positive feedback loop promoting pseudopod formation. Here, we show that neutrophils lacking P55 form multiple transient pseudopods at the sides and back of the cell upon stimulation. P55 is required for limiting the pseudopod in the direction of chemoattractant. As a result, these neutrophils do not migrate efficiently up a chemotactic gradient in vitro. Biochemical analysis indicates that total F-actin polymerization and total Rac activation is similar between wild type and P55 knockout neutrophils. However, we found that phosphorylation of AKT, the major kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-PIP3 pathway, is almost completely blocked in P55 knockout neutrophils. This finding suggests that P55 exerts its functional effect by regulating PIP3 accumulation or its localization at the membrane, which is responsible for amplification of the frontness signal and stability of the leading edge pseudopod. Consistent with this finding, the P55 null mice are significantly more susceptible to spontaneous and induced infections. Taken together, we have identified P55 as a novel mediator of the frontness signal in neutrophils that promotes polarization and efficient chemotaxis.
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cDNA Sequence and Genomic Structure of the Murine P55 (Mpp1) Gene
Genomics, 1996Co-Authors: Bruce Elder, Jane Gitschier, Athar H Chishti, Aida MetzenbergAbstract:Abstract MPP1 is an X-linked human gene encoding a heavily palmitoylated membrane Protein (P55) with homology to the Drosophila tumor suppressor gene lethal(1) discs-large. As a first step toward studying the effects of mutations in this gene in a mammalian system, the nucleotide sequence of the mouse Mpp1 cDNA has been determined along with the intron–exon boundaries. Mpp1 is ubiquitously expressed and encodes a P55 Protein of 466 amino acids with 93 and 65% identity to the human and puffer fish ( Fugu rubripes ) P55 sequences, respectively. The genomic structure of the Mpp1 gene is likewise conserved with 12 exons. The location of the Mpp1 gene, on the X chromosome, is also conserved between the human and the mouse. Conservation of the Mpp1 gene between mouse and human gives support to the notion that construction and study of a mouse knockout model may help establish the function of the human MPP1 gene, a potential tumor suppressor gene.
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evidence that red blood cell Protein P55 may participate in the skeleton membrane linkage that involves Protein 4 1 and glycophorin c
Blood, 1993Co-Authors: N Alloisio, J. Delaunay, Dalla N Venezia, A Rana, K Andrabi, P Texier, F Gilsanz, J P Cartron, Athar H ChishtiAbstract:Human erythrocyte P55 is a peripheral membrane Protein that contains three distinct domains in its primary structure: an N-terminal domain, an SH3 motif, and a C-terminal guanylate kinase domain. We used naturally mutated red blood cells (RBCs) with primary genetic defects resulting in the absence of Protein 4.1 (4.1[-] hereditary elliptocytosis) or glycophorin C (Leach elliptocytosis). The absence of either Protein was associated with the absence of P55. On a stoichiometric basis, the reduction in glycophorin C (about 80%) was concomitant to the lack of P55 in RBCs devoid of Protein 4.1. Similarly, the reduction of Protein 4.1 (about 20%) was equivalent to the absence of P55 in RBCs devoid of glycophorin C. These correlations suggest that P55 is associated, in precise proportions, with the Protein 4.1-glycophorin-C complex, linking the skeleton and the membrane. The Protein 4.1-glycophorin-C cross-bridge is known to be critically important for the stability and mechanical properties of human RBC plasma membrane. Because isoforms of Protein 4.1, glycophorin C, and P55 exist in many tissues, these results provide evidence of a linkage between the skeleton and the membrane that may have implications in many nonerythroid cells.
Yi Zeng - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 P55 gag Protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro
Cell Biology International, 2017Co-Authors: Yahong Yuan, Shanshan Zhao, Xiaoli Wang, Zhiping Teng, Dong Sheng Li, Yi ZengAbstract:Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the BM mesenchymal stem cells (BMSCs) can be impacted by HIV Proteins that are released by infected cells within BM. In this study, we tested whether HIV Protein P55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with P55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon ). Then, we analyzed the hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability, and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon , BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by P55-gag resulted in decreased hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.
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HIV‐1 P55‐gag Protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro
Cell Biology International, 2017Co-Authors: Yahong Yuan, Shanshan Zhao, Xiaoli Wang, Zhiping Teng, Dong Sheng Li, Yi ZengAbstract:Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the bone marrow mesenchymal stem cells (BMSCs) can be impacted by HIV Proteins that are released by infected cells within BM. In this study, we tested whether HIV Protein P55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with P55-gag (BMSCgag) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon). Then, we analyzed the .hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon, BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by P55-gag resulted in decreased .hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.
P B Nirmala - One of the best experts on this subject based on the ideXlab platform.
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a 55 kda Protein P55 of the goat uterus mediates nuclear transport of the estrogen receptor ii details of the transport mechanism
Archives of Biochemistry and Biophysics, 1995Co-Authors: P B Nirmala, R V ThampanAbstract:Abstract A 55-kDa Protein (P55) that mediates the transport of the estrogen receptor (ER) from the cytoplasm to the nucleus has been purified to homogeneity from goat uterine cytosol. Using this pure Protein, some of the aspects of the mechanisms associated with the transport of the ER to the nucleus have been elucidated. The mechanism of ER transport into the nucleus can be separated into two steps: the P55-mediated transport and binding of ER to the nuclear membrane, followed by an ATP-dependent, 14-kDa Protein(s)-mediated translocation of ER into the nucleus. The P55 has inherent ATPase activity and it is proposed that the energy released during this ATP hydrolysis is utilized in the nuclear transport of the ER.
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a 55 kda Protein P55 of the goat uterus mediates nuclear transport of the estrogen receptor i purification and characterization
Archives of Biochemistry and Biophysics, 1995Co-Authors: P B Nirmala, R V ThampanAbstract:Abstract A 55-kDa Protein (P55), purified from the goat uterine cytosol, transports estrogen receptor (ER) into the nucleus. Selective elution of this Protein from a column of estrogen receptor-Sepharose using buffers containing high concentrations of lysine and the high affinity with which it binds to poly-L-lysine-Sepharose indicate that it recognizes a lysine-rich region in the ER. Its strong binding to tubulin-Sepharose and actin-Sepharose is indicative of a role that the cytoskeletal elements play in the nuclear transport of the ER, mediated by P55, This Protein can be purified in a single step following chromatography of the uterine cytosol on a column of actin-Sepharose. Antibodies raised against poly-L-aspartic acid cross-reacted with P55 and inhibited the nuclear transport of the ER, The binding of P55 to a heterologous nuclear localization sequence of the SV40 large T suggests that it may also be involved in the transport of Proteins other than the ER.
Yahong Yuan - One of the best experts on this subject based on the ideXlab platform.
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hiv 1 P55 gag Protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro
Cell Biology International, 2017Co-Authors: Yahong Yuan, Shanshan Zhao, Xiaoli Wang, Zhiping Teng, Dong Sheng Li, Yi ZengAbstract:Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the BM mesenchymal stem cells (BMSCs) can be impacted by HIV Proteins that are released by infected cells within BM. In this study, we tested whether HIV Protein P55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with P55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon ). Then, we analyzed the hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability, and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon , BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by P55-gag resulted in decreased hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.
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HIV‐1 P55‐gag Protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro
Cell Biology International, 2017Co-Authors: Yahong Yuan, Shanshan Zhao, Xiaoli Wang, Zhiping Teng, Dong Sheng Li, Yi ZengAbstract:Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the bone marrow mesenchymal stem cells (BMSCs) can be impacted by HIV Proteins that are released by infected cells within BM. In this study, we tested whether HIV Protein P55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with P55-gag (BMSCgag) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon). Then, we analyzed the .hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon, BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by P55-gag resulted in decreased .hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.
