| http://purl.uniprot.org/citations/12975377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12975377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12975377 | http://www.w3.org/2000/01/rdf-schema#comment | "Kinase suppressor of Ras (KSR) is an integral and conserved component of the Ras signaling pathway. Although KSR is a positive regulator of the Ras/mitogen-activated protein (MAP) kinase pathway, the role of KSR in Cot-mediated MAPK activation has not been identified. The serine/threonine kinase Cot (also known as Tpl2) is a member of the MAP kinase kinase kinase (MAP3K) family that is known to regulate oncogenic and inflammatory pathways; however, the mechanism(s) of its regulation are not precisely known. In this report, we identify an 830-amino acid novel human KSR, designated hKSR-2, using predictions from genomic data base mining based on the structural profile of the KSR kinase domain. We show that, similar to the known human KSR, hKSR-2 co-immunoprecipitates with many signaling components of the Ras/MAPK pathway, including Ras, Raf, MEK-1, and ERK-1/2. In addition, we demonstrate that hKSR-2 co-immunoprecipitates with Cot and that co-expression of hKSR-2 with Cot significantly reduces Cot-mediated MAPK and NF-kappaB activation. This inhibition is specific to Cot, because Ras-induced ERK and IkappaB kinase-induced NF-kappaB activation are not significantly affected by hKSR-2 co-expression. Moreover, Cot-induced interleukin-8 production in HeLa cells is almost completely inhibited by the concurrent expression of hKSR-2, whereas transforming growth factor beta-activated kinase 1 (TAK1)/TAK1-binding protein 1 (TAB1)-induced interleukin-8 production is not affected by hKSR-2 co-expression. Taken together, these results indicate that hKSR-2, a new member of the KSR family, negatively regulates Cot-mediated MAP kinase and NF-kappaB pathway signaling."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m306002200"xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m306002200"xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Liu W."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Liu W."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Wu L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Wu L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Lin L.-L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Lin L.-L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Cuozzo J.W."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Cuozzo J.W."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Hall J.P."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Hall J.P."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Channavajhala P.L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/author | "Channavajhala P.L."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/pages | "47089-47097"xsd:string |
| http://purl.uniprot.org/citations/12975377 | http://purl.uniprot.org/core/pages | "47089-47097"xsd:string |