| http://purl.uniprot.org/citations/15689566 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15689566 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15689566 | http://www.w3.org/2000/01/rdf-schema#comment | "Intracellular Ca2+ and protein phosphorylation play pivotal roles in long-term potentiation (LTP), a cellular model of learning and memory. Ca2+ regulates multiple intracellular pathways, including the calmodulin-dependent kinases (CaMKs) and the ERKs (extracellular signal-regulated kinases), both of which are required for LTP. However, the mechanism by which Ca2+ activates ERK during LTP remains unknown. Here, we describe a requirement for the CaMK-kinase (CaMKK) pathway upstream of ERK in LTP induction. Both the pharmacological inhibitor of CaMKK, STO-609, and dominant-negative CaMKI (dnCaMKI), a downstream target of CaMKK, blocked neuronal NMDA receptor-dependent ERK activation. In contrast, an inhibitor of CaMKII and nuclear-localized dnCaMKIV had no effect on ERK activation. NMDA receptor-dependent LTP induction robustly activated CaMKI, the Ca2+-stimulated Ras activator Ras-GRF1 (Ras-guanyl-nucleotide releasing factor), and ERK. STO-609 blocked the activation of all three enzymes during LTP without affecting basal synaptic transmission, activation of CaMKII, or cAMP-dependent activation of ERK. LTP induction itself was suppressed 50% by STO-609 in a manner identical to the ERK inhibitor U0126: either inhibitor occluded the effect of the other, suggesting they are part of the same signaling pathway in LTP induction. STO-609 also suppressed regulatory phosphorylation of two downstream ERK targets during LTP, the general translation factors eIF4E (eukaryotic initiation factor 4) and its binding protein 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). These data indicate an essential role for CaMKK and CaMKI to link NMDA receptor-mediated Ca2+ elevation with ERK-dependent LTP."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.4086-04.2005"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.4086-04.2005"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Schmitt J.M."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Schmitt J.M."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Saneyoshi T."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Saneyoshi T."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Soderling T.R."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Soderling T.R."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Guire E.S."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/author | "Guire E.S."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/name | "J. Neurosci."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/name | "J. Neurosci."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/pages | "1281-1290"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/pages | "1281-1290"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/title | "Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/title | "Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation."xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/volume | "25"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://purl.uniprot.org/core/volume | "25"xsd:string |
| http://purl.uniprot.org/citations/15689566 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15689566 |
| http://purl.uniprot.org/citations/15689566 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15689566 |