PubMed:15192701 JSONTXT

{"project":"test_HZAU_BioNLP","denotations":[{"id":"T1","span":{"begin":35,"end":40},"obj":"https://www.uniprot.org/uniprot/P49841"},{"id":"T2","span":{"begin":944,"end":949},"obj":"https://www.uniprot.org/uniprot/P49841"},{"id":"T3","span":{"begin":963,"end":968},"obj":"https://www.uniprot.org/uniprot/P49841"},{"id":"T4","span":{"begin":1162,"end":1167},"obj":"https://www.uniprot.org/uniprot/P49841"}],"text":"PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.\nPhosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors. Pharmacological and genetic evidence indicates that PS1 acts upstream of Akt, at or before PI3K kinase. PS1 forms complexes with the p85 subunit of PI3K and promotes cadherin/PI3K association. Furthermore, conditions that inhibit this association prevent the PS1-induced PI3K/Akt activation, indicating that PS1 stimulates PI3K/Akt signaling by promoting cadherin/PI3K association. By activating PI3K/Akt signaling, PS1 promotes phosphorylation/inactivation of glycogen synthase kinase-3 (GSK-3), suppresses GSK-3-dependent phosphorylation of tau at residues overphosphorylated in AD and prevents apoptosis of confluent cells. PS1 FAD mutations inhibit the PS1-dependent PI3K/Akt activation, thus promoting GSK-3 activity and tau overphosphorylation at AD-related residues. Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15192701-0#14#18#gene5290","span":{"begin":14,"end":18},"obj":"gene5290"},{"id":"15192701-0#14#18#gene5291","span":{"begin":14,"end":18},"obj":"gene5291"},{"id":"15192701-0#14#18#gene5293","span":{"begin":14,"end":18},"obj":"gene5293"},{"id":"15192701-0#14#18#gene5294","span":{"begin":14,"end":18},"obj":"gene5294"},{"id":"15192701-0#90#93#diseaseC0276496","span":{"begin":90,"end":93},"obj":"diseaseC0276496"},{"id":"15192701-9#98#102#gene5290","span":{"begin":1327,"end":1331},"obj":"gene5290"},{"id":"15192701-9#98#102#gene5291","span":{"begin":1327,"end":1331},"obj":"gene5291"},{"id":"15192701-9#98#102#gene5293","span":{"begin":1327,"end":1331},"obj":"gene5293"},{"id":"15192701-9#98#102#gene5294","span":{"begin":1327,"end":1331},"obj":"gene5294"},{"id":"15192701-9#67#69#diseaseC0002395","span":{"begin":1296,"end":1298},"obj":"diseaseC0002395"}],"relations":[{"id":"14#18#gene529090#93#diseaseC0276496","pred":"associated_with","subj":"15192701-0#14#18#gene5290","obj":"15192701-0#90#93#diseaseC0276496"},{"id":"14#18#gene529190#93#diseaseC0276496","pred":"associated_with","subj":"15192701-0#14#18#gene5291","obj":"15192701-0#90#93#diseaseC0276496"},{"id":"14#18#gene529390#93#diseaseC0276496","pred":"associated_with","subj":"15192701-0#14#18#gene5293","obj":"15192701-0#90#93#diseaseC0276496"},{"id":"14#18#gene529490#93#diseaseC0276496","pred":"associated_with","subj":"15192701-0#14#18#gene5294","obj":"15192701-0#90#93#diseaseC0276496"},{"id":"98#102#gene529067#69#diseaseC0002395","pred":"associated_with","subj":"15192701-9#98#102#gene5290","obj":"15192701-9#67#69#diseaseC0002395"},{"id":"98#102#gene529167#69#diseaseC0002395","pred":"associated_with","subj":"15192701-9#98#102#gene5291","obj":"15192701-9#67#69#diseaseC0002395"},{"id":"98#102#gene529367#69#diseaseC0002395","pred":"associated_with","subj":"15192701-9#98#102#gene5293","obj":"15192701-9#67#69#diseaseC0002395"},{"id":"98#102#gene529467#69#diseaseC0002395","pred":"associated_with","subj":"15192701-9#98#102#gene5294","obj":"15192701-9#67#69#diseaseC0002395"}],"text":"PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.\nPhosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors. Pharmacological and genetic evidence indicates that PS1 acts upstream of Akt, at or before PI3K kinase. PS1 forms complexes with the p85 subunit of PI3K and promotes cadherin/PI3K association. Furthermore, conditions that inhibit this association prevent the PS1-induced PI3K/Akt activation, indicating that PS1 stimulates PI3K/Akt signaling by promoting cadherin/PI3K association. By activating PI3K/Akt signaling, PS1 promotes phosphorylation/inactivation of glycogen synthase kinase-3 (GSK-3), suppresses GSK-3-dependent phosphorylation of tau at residues overphosphorylated in AD and prevents apoptosis of confluent cells. PS1 FAD mutations inhibit the PS1-dependent PI3K/Akt activation, thus promoting GSK-3 activity and tau overphosphorylation at AD-related residues. Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1327,"end":1331},"obj":"gene:5294"},{"id":"T1","span":{"begin":1296,"end":1298},"obj":"disease:C0002395"},{"id":"T2","span":{"begin":1327,"end":1331},"obj":"gene:5293"},{"id":"T3","span":{"begin":1296,"end":1298},"obj":"disease:C0002395"},{"id":"T4","span":{"begin":1327,"end":1331},"obj":"gene:5290"},{"id":"T5","span":{"begin":1296,"end":1298},"obj":"disease:C0002395"},{"id":"T6","span":{"begin":1327,"end":1331},"obj":"gene:5291"},{"id":"T7","span":{"begin":1296,"end":1298},"obj":"disease:C0002395"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.\nPhosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors. Pharmacological and genetic evidence indicates that PS1 acts upstream of Akt, at or before PI3K kinase. PS1 forms complexes with the p85 subunit of PI3K and promotes cadherin/PI3K association. Furthermore, conditions that inhibit this association prevent the PS1-induced PI3K/Akt activation, indicating that PS1 stimulates PI3K/Akt signaling by promoting cadherin/PI3K association. By activating PI3K/Akt signaling, PS1 promotes phosphorylation/inactivation of glycogen synthase kinase-3 (GSK-3), suppresses GSK-3-dependent phosphorylation of tau at residues overphosphorylated in AD and prevents apoptosis of confluent cells. PS1 FAD mutations inhibit the PS1-dependent PI3K/Akt activation, thus promoting GSK-3 activity and tau overphosphorylation at AD-related residues. Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway."}