| http://purl.uniprot.org/citations/23509299 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23509299 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23509299 | http://www.w3.org/2000/01/rdf-schema#comment | "V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) is a key activator of the ERK pathway and is a target for cross-regulation of this pathway by the cAMP signaling system. The cAMP-activated protein kinase, PKA, inhibits Raf-1 by phosphorylation on S259. Here, we show that the cAMP-degrading phosphodiesterase-8A (PDE8A) associates with Raf-1 to protect it from inhibitory phosphorylation by PKA, thereby enhancing Raf-1's ability to stimulate ERK signaling. PDE8A binds to Raf-1 with high (picomolar) affinity. Mapping of the interaction domain on PDE8A using peptide array technology identified amino acids 454-465 as the main binding site, which could be disrupted by mutation. A cell-permeable peptide corresponding to this region disrupted the PDE8A/Raf-1 interaction in cells, thereby reducing ERK activation and the cellular response to EGF. Overexpression of a catalytically inactive PDE8A in cells displayed a dominant negative phenotype on ERK activation. These effects were recapitulated at the organism level in genetically modified (PDE8A(-/-)) mice. Similarly, PDE8 deletion in Drosophila melanogaster reduced basal ERK activation and sensitized flies to stress-induced death. We propose that PDE8A is a physiological regulator of Raf-1 signaling in some cells."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1303004110"xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1303004110"xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Kolch W."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Kolch W."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Brown K.M."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Brown K.M."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Houslay M.D."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Houslay M.D."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Romano D."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Romano D."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Beavo J.A."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Beavo J.A."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Baillie G.S."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Baillie G.S."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Huston E."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Huston E."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Zimmermann B."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Zimmermann B."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Davies S.A."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Davies S.A."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Day J.P."xsd:string |
| http://purl.uniprot.org/citations/23509299 | http://purl.uniprot.org/core/author | "Day J.P."xsd:string |