The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
K L Guan - One of the best experts on this subject based on the ideXlab platform.
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differential regulation of fus3 map kinase by tyrosine specific phosphatases ptp2 ptp3 and dual specificity phosphatase msg5 in saccharomyces cerevisiae
Genes & Development, 1997Co-Authors: X L Zhan, Robert J Deschenes, K L GuanAbstract:: The Saccharomyces cerevisiae mating pheromone response is mediated by activation of a MAP kinase (Fus3p and Kss1p) signaling pathway. Pheromone stimulation causes cell cycle arrest. Therefore, inactivation of the Fus3p and Kss1p MAP kinases is required during recovery phase for the resumption of cell growth. We have isolated a novel protein tyrosine phosphatase gene, PTP3, as a negative regulator of this pathway. Ptp3p directly dephosphorylates and inactivates Fus3p MAP kinase in vitro. Multicopy PTP3 represses pheromone-induced transcription and promotes recovery. In contrast, disruption of PTP3 in combination with its homolog PTP2 results in constitutive tyrosine phosphorylation, enhanced kinase activity of Fus3p MAP kinase on stimulation, and delayed recovery from the cell cycle arrest. Both tyrosine phosphorylation and kinase activity of Fus3p are further increased by disruption of PTP3 and PTP2 in combination with MSG5, which encodes a dual-specificity phosphatase. Cells deleted for all three of the phosphatases (ptp2delta ptp3delta msg5delta) are hypersensitive to pheromone and exhibit a Severe Defect in recovery from pheromone-induced growth arrest. Our data indicate that Ptp3p is the major phosphatase responsible for tyrosine dephosphorylation of Fus3p to maintain a low basal activity; it also has important roles, along with Msg5p, in inactivation of Fus3p following pheromone stimulation. These data present the first evidence for a coordinated regulation of MAP kinase function through differential actions of protein tyrosine phosphatases and a dual-specificity phosphatase.
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Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae.
Genes & Development, 1997Co-Authors: X L Zhan, Robert J Deschenes, K L GuanAbstract:: The Saccharomyces cerevisiae mating pheromone response is mediated by activation of a MAP kinase (Fus3p and Kss1p) signaling pathway. Pheromone stimulation causes cell cycle arrest. Therefore, inactivation of the Fus3p and Kss1p MAP kinases is required during recovery phase for the resumption of cell growth. We have isolated a novel protein tyrosine phosphatase gene, PTP3, as a negative regulator of this pathway. Ptp3p directly dephosphorylates and inactivates Fus3p MAP kinase in vitro. Multicopy PTP3 represses pheromone-induced transcription and promotes recovery. In contrast, disruption of PTP3 in combination with its homolog PTP2 results in constitutive tyrosine phosphorylation, enhanced kinase activity of Fus3p MAP kinase on stimulation, and delayed recovery from the cell cycle arrest. Both tyrosine phosphorylation and kinase activity of Fus3p are further increased by disruption of PTP3 and PTP2 in combination with MSG5, which encodes a dual-specificity phosphatase. Cells deleted for all three of the phosphatases (ptp2delta ptp3delta msg5delta) are hypersensitive to pheromone and exhibit a Severe Defect in recovery from pheromone-induced growth arrest. Our data indicate that Ptp3p is the major phosphatase responsible for tyrosine dephosphorylation of Fus3p to maintain a low basal activity; it also has important roles, along with Msg5p, in inactivation of Fus3p following pheromone stimulation. These data present the first evidence for a coordinated regulation of MAP kinase function through differential actions of protein tyrosine phosphatases and a dual-specificity phosphatase.
Sioban B Keel - One of the best experts on this subject based on the ideXlab platform.
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mice lacking the sodium dependent phosphate import protein pit1 slc20a1 have a Severe Defect in terminal erythroid differentiation and early b cell development
Experimental Hematology, 2013Co-Authors: Marilyn Sanchezbonilla, Mathew Crouthamel, Cecilia M Giachelli, Sioban B KeelAbstract:Phosphate is critical in multiple biological processes (phosphorylation reactions, ATP production, and DNA structure and synthesis). It remains unclear how individual cells initially sense changes in phosphate availability and the cellular consequences of these changes. PiT1 (or SLC20A1) is a constitutively expressed, high-affinity sodium-dependent phosphate import protein. In vitro data suggest that PiT1 serves a direct role in mediating cellular proliferation; its role in vivo is unclear. We have discovered that mice lacking PiT1 develop a profound underproduction anemia characterized by mild macrocytosis, dyserythropoiesis, increased apoptosis, and a near complete block in terminal erythroid differentiation. In addition, the animals are Severely B cell lymphopenic because of a Defect in pro–B cell development and mildly neutropenic. The phenotype is intrinsic to the hematopoietic system, is associated with a Defect in cell cycle progression, and occurs in the absence of changes in serum phosphate or calcium concentrations and independently of a change in cellular phosphate uptake. The severity of the anemia and block in terminal erythroid differentiation and B cell lymphopenia are striking and suggest that PiT1 serves a fundamental and nonredundant role in murine terminal erythroid differentiation and B cell development. Intriguingly, as the anemia mimics the ineffective erythropoiesis in some low-grade human myelodysplastic syndromes, this murine model might also provide pathologic insight into these disorders.
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mice lacking the sodium dependent phosphate import protein pit 1 have a Severe Defect in terminal erythroid differentiation
Blood, 2011Co-Authors: Marilyn Sanchezbonilla, Yan Wang, Mathew Crouthamel, Cecilia M Giachelli, Sioban B KeelAbstract:Abstract 681 Phosphate is the second most abundant mineral in the human body and plays an essential role in phospholipids, nucleoproteins and nucleic acids, bone mineralization, the storage and liberation of metabolic energy, and enzyme activity. While our understanding of the mechanisms of phosphate homeostasis has advanced, little is known about how the body initially senses changes in phosphate concentration or the downstream biological processes regulated by these concentration changes. Among the three families of membrane mammalian sodium-phosphate import proteins, PiT-1 and its family member, PiT-2, have the highest substrate affinity. PiT-1 is broadly expressed (Proc Nat Acad Sci, 91,7071-75;1994). Cell line models suggest PiT-1 functions in cellular phosphate homeostasis and vascular calcification (PLoS One, 5,e9148;2010). To determine its in vivo role, two groups have generated PiT-1-null mice. Constitutive deletion of PiT-1 results in embryonic lethality at midgestation and mutant embryos display pale livers (the site of fetal erythropoiesis) with increased apoptosis and reduced hematopoietic colony growth (PLoS One, 5, e9148:2010 & Genesis, 47,858-863;2009). These findings suggest that PiT-1 is required for normal erythropoiesis or hematopoiesis, and provided the rationale to characterize the hematopoietic phenotype of post-natal mice lacking PiT-1. We have discovered that mice lacking PiT-1 have markedly abnormal erythropoiesis which models low-grade myeodysplastic syndromes(MDS). MDS comprise a varied group of malignant stem cell disorders characterized by ineffective blood cell production resulting in increased apoptosis and dysplasia in bone marrow progenitor cells and peripheral blood cytopenias. The precise molecular basis of MDS remains unknown and its wide phenotype likely reflects multiple pathophysiologies. We bred mice expressing a conditional PiT-1 allele (PiT-1flox, gift from the Giachelli Lab) to mice expressing the Mx-Cre transgene to generate a viable null mouse for study. PiT-1-deleted mice develop a Severe hypoproliferative, macrocytic anemia (HGB 4.5g/dL±0.3 vs. 13.3±1.0, p Disclosures: No relevant conflicts of interest to declare.
X L Zhan - One of the best experts on this subject based on the ideXlab platform.
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differential regulation of fus3 map kinase by tyrosine specific phosphatases ptp2 ptp3 and dual specificity phosphatase msg5 in saccharomyces cerevisiae
Genes & Development, 1997Co-Authors: X L Zhan, Robert J Deschenes, K L GuanAbstract:: The Saccharomyces cerevisiae mating pheromone response is mediated by activation of a MAP kinase (Fus3p and Kss1p) signaling pathway. Pheromone stimulation causes cell cycle arrest. Therefore, inactivation of the Fus3p and Kss1p MAP kinases is required during recovery phase for the resumption of cell growth. We have isolated a novel protein tyrosine phosphatase gene, PTP3, as a negative regulator of this pathway. Ptp3p directly dephosphorylates and inactivates Fus3p MAP kinase in vitro. Multicopy PTP3 represses pheromone-induced transcription and promotes recovery. In contrast, disruption of PTP3 in combination with its homolog PTP2 results in constitutive tyrosine phosphorylation, enhanced kinase activity of Fus3p MAP kinase on stimulation, and delayed recovery from the cell cycle arrest. Both tyrosine phosphorylation and kinase activity of Fus3p are further increased by disruption of PTP3 and PTP2 in combination with MSG5, which encodes a dual-specificity phosphatase. Cells deleted for all three of the phosphatases (ptp2delta ptp3delta msg5delta) are hypersensitive to pheromone and exhibit a Severe Defect in recovery from pheromone-induced growth arrest. Our data indicate that Ptp3p is the major phosphatase responsible for tyrosine dephosphorylation of Fus3p to maintain a low basal activity; it also has important roles, along with Msg5p, in inactivation of Fus3p following pheromone stimulation. These data present the first evidence for a coordinated regulation of MAP kinase function through differential actions of protein tyrosine phosphatases and a dual-specificity phosphatase.
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Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae.
Genes & Development, 1997Co-Authors: X L Zhan, Robert J Deschenes, K L GuanAbstract:: The Saccharomyces cerevisiae mating pheromone response is mediated by activation of a MAP kinase (Fus3p and Kss1p) signaling pathway. Pheromone stimulation causes cell cycle arrest. Therefore, inactivation of the Fus3p and Kss1p MAP kinases is required during recovery phase for the resumption of cell growth. We have isolated a novel protein tyrosine phosphatase gene, PTP3, as a negative regulator of this pathway. Ptp3p directly dephosphorylates and inactivates Fus3p MAP kinase in vitro. Multicopy PTP3 represses pheromone-induced transcription and promotes recovery. In contrast, disruption of PTP3 in combination with its homolog PTP2 results in constitutive tyrosine phosphorylation, enhanced kinase activity of Fus3p MAP kinase on stimulation, and delayed recovery from the cell cycle arrest. Both tyrosine phosphorylation and kinase activity of Fus3p are further increased by disruption of PTP3 and PTP2 in combination with MSG5, which encodes a dual-specificity phosphatase. Cells deleted for all three of the phosphatases (ptp2delta ptp3delta msg5delta) are hypersensitive to pheromone and exhibit a Severe Defect in recovery from pheromone-induced growth arrest. Our data indicate that Ptp3p is the major phosphatase responsible for tyrosine dephosphorylation of Fus3p to maintain a low basal activity; it also has important roles, along with Msg5p, in inactivation of Fus3p following pheromone stimulation. These data present the first evidence for a coordinated regulation of MAP kinase function through differential actions of protein tyrosine phosphatases and a dual-specificity phosphatase.
Marilyn Sanchezbonilla - One of the best experts on this subject based on the ideXlab platform.
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mice lacking the sodium dependent phosphate import protein pit1 slc20a1 have a Severe Defect in terminal erythroid differentiation and early b cell development
Experimental Hematology, 2013Co-Authors: Marilyn Sanchezbonilla, Mathew Crouthamel, Cecilia M Giachelli, Sioban B KeelAbstract:Phosphate is critical in multiple biological processes (phosphorylation reactions, ATP production, and DNA structure and synthesis). It remains unclear how individual cells initially sense changes in phosphate availability and the cellular consequences of these changes. PiT1 (or SLC20A1) is a constitutively expressed, high-affinity sodium-dependent phosphate import protein. In vitro data suggest that PiT1 serves a direct role in mediating cellular proliferation; its role in vivo is unclear. We have discovered that mice lacking PiT1 develop a profound underproduction anemia characterized by mild macrocytosis, dyserythropoiesis, increased apoptosis, and a near complete block in terminal erythroid differentiation. In addition, the animals are Severely B cell lymphopenic because of a Defect in pro–B cell development and mildly neutropenic. The phenotype is intrinsic to the hematopoietic system, is associated with a Defect in cell cycle progression, and occurs in the absence of changes in serum phosphate or calcium concentrations and independently of a change in cellular phosphate uptake. The severity of the anemia and block in terminal erythroid differentiation and B cell lymphopenia are striking and suggest that PiT1 serves a fundamental and nonredundant role in murine terminal erythroid differentiation and B cell development. Intriguingly, as the anemia mimics the ineffective erythropoiesis in some low-grade human myelodysplastic syndromes, this murine model might also provide pathologic insight into these disorders.
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mice lacking the sodium dependent phosphate import protein pit 1 have a Severe Defect in terminal erythroid differentiation
Blood, 2011Co-Authors: Marilyn Sanchezbonilla, Yan Wang, Mathew Crouthamel, Cecilia M Giachelli, Sioban B KeelAbstract:Abstract 681 Phosphate is the second most abundant mineral in the human body and plays an essential role in phospholipids, nucleoproteins and nucleic acids, bone mineralization, the storage and liberation of metabolic energy, and enzyme activity. While our understanding of the mechanisms of phosphate homeostasis has advanced, little is known about how the body initially senses changes in phosphate concentration or the downstream biological processes regulated by these concentration changes. Among the three families of membrane mammalian sodium-phosphate import proteins, PiT-1 and its family member, PiT-2, have the highest substrate affinity. PiT-1 is broadly expressed (Proc Nat Acad Sci, 91,7071-75;1994). Cell line models suggest PiT-1 functions in cellular phosphate homeostasis and vascular calcification (PLoS One, 5,e9148;2010). To determine its in vivo role, two groups have generated PiT-1-null mice. Constitutive deletion of PiT-1 results in embryonic lethality at midgestation and mutant embryos display pale livers (the site of fetal erythropoiesis) with increased apoptosis and reduced hematopoietic colony growth (PLoS One, 5, e9148:2010 & Genesis, 47,858-863;2009). These findings suggest that PiT-1 is required for normal erythropoiesis or hematopoiesis, and provided the rationale to characterize the hematopoietic phenotype of post-natal mice lacking PiT-1. We have discovered that mice lacking PiT-1 have markedly abnormal erythropoiesis which models low-grade myeodysplastic syndromes(MDS). MDS comprise a varied group of malignant stem cell disorders characterized by ineffective blood cell production resulting in increased apoptosis and dysplasia in bone marrow progenitor cells and peripheral blood cytopenias. The precise molecular basis of MDS remains unknown and its wide phenotype likely reflects multiple pathophysiologies. We bred mice expressing a conditional PiT-1 allele (PiT-1flox, gift from the Giachelli Lab) to mice expressing the Mx-Cre transgene to generate a viable null mouse for study. PiT-1-deleted mice develop a Severe hypoproliferative, macrocytic anemia (HGB 4.5g/dL±0.3 vs. 13.3±1.0, p Disclosures: No relevant conflicts of interest to declare.
H Ma - One of the best experts on this subject based on the ideXlab platform.
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Male meiotic spindle lengths in normal and mutant arabidopsis cells.
Plant physiology, 2001Co-Authors: Ming Yang, H MaAbstract:Spindle elongation is crucial to normal chromosome separation in eukaryotes; in particular, it is required for or associated with the extension of distance between spindle poles and the further moving apart of the already separated chromosomes. However, little is known about the relationship between spindle elongation and the status of chromosome separation, and it is unknown whether spindle elongation in different organisms shares any quantitative feature. The Arabidopsis ask1-1 mutant might be a unique material for addressing these questions because it appears to have functional spindles, but a Severe Defect in homolog separation at male anaphase I (M. Yang, Y. Hu, M. Lodhi, W.R. McCombie, H Ma [1999] Proc Natl Acad Sci USA 96: 11416-11421). We have characterized male meiotic spindle lengths in wild-type and the ask1-1 mutant plants. We observed that during meiosis I some ask1-1 cells had spindles that were similar in length to fully elongated normal spindles, but the chromosomes in these cells did not show appreciable movement from the equator. Furthermore, greater movement of chromosomes from the equator was usually found in the ask1-1 cells that had longer than normal spindles. These results suggest that additional elongation of ask1-1 spindles occurred; one possible reason for the extra-long spindles may be that it is a consequence of chromosome non-separation. We also found that normal and ask1-1 spindle lengths are clustered at discrete values, and their differences are of multiples of 0.7 microm. A search of the literature revealed that in each of several organisms, spindle lengths also differ by multiples of 0.7 microm. These findings strongly suggest that the spindle elongates in response to status of chromosome separation, and perhaps there are conserved mechanisms controlling the extent of spindle elongation.
