Results
Your Query
▶
▶
| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/17565996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17565996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17565996 | http://www.w3.org/2000/01/rdf-schema#comment | "Apoptosis is an essential mechanism for the maintenance of somatic tissues, and when dysregulated can lead to numerous pathological conditions. G proteins regulate apoptosis in addition to other cellular functions, but the roles of specific G proteins in apoptosis signaling are not well characterized. Galpha12 stimulates protein phosphatase 2A (PP2A), a serine/threonine phosphatase that modulates essential signaling pathways, including apoptosis. Herein, we examined whether Galpha12 regulates apoptosis in epithelial cells. Inducible expression of Galpha12 or constitutively active (QL)alpha12 in Madin-Darby canine kidney cells led to increased apoptosis with expression of QLalpha12, but not Galpha12. Inducing QLalpha12 led to degradation of the anti-apoptotic protein Bcl-2 (via the proteasome pathway), increased JNK activity, and up-regulated IkappaBalpha protein levels, a potent stimulator of apoptosis. Furthermore, the QLalpha12-stimulated activation of JNK was blocked by inhibiting PP2A. To characterize endogenous Galpha12 signaling pathways, non-transfected MDCK-II and HEK293 cells were stimulated with thrombin. Thrombin activated endogenous Galpha12 (confirmed by GST-tetratricopeptide repeat (TPR) pull-downs) and stimulated apoptosis in both cell types. The mechanisms of thrombin-stimulated apoptosis through endogenous Galpha12 were nearly identical to the mechanisms identified in QLalpha12-MDCK cells and included loss of Bcl-2, JNK activation, and up-regulation of IkappaBalpha. Knockdown of the PP2A catalytic subunit in HEK293 cells inhibited thrombin-stimulated apoptosis, prevented JNK activation, and blocked Bcl-2 degradation. In summary, Galpha12 has a major role in regulating epithelial cell apoptosis through PP2A and JNK activation leading to loss of Bcl-2 protein expression. Targeting these pathways in vivo may lead to new therapeutic strategies for a variety of disease processes."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m702804200"xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m702804200"xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Denker B.M."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Denker B.M."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Yanamadala V."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Yanamadala V."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Kong T."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Kong T."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Negoro H."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Negoro H."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Gunaratnam L."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/author | "Gunaratnam L."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/pages | "24352-24363"xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/pages | "24352-24363"xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/title | "Galpha12 stimulates apoptosis in epithelial cells through JNK1-mediated Bcl-2 degradation and up-regulation of IkappaBalpha."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/title | "Galpha12 stimulates apoptosis in epithelial cells through JNK1-mediated Bcl-2 degradation and up-regulation of IkappaBalpha."xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/volume | "282"xsd:string |
| http://purl.uniprot.org/citations/17565996 | http://purl.uniprot.org/core/volume | "282"xsd:string |