http://purl.uniprot.org/citations/19073898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19073898 | http://www.w3.org/2000/01/rdf-schema#comment | "Stimulation of numerous G protein-coupled receptors leads to the elevation of intracellular concentrations of cAMP, which subsequently activates the PKA pathway. Specificity of the PKA signaling module is determined by a sophisticated subcellular targeting network that directs the spatiotemporal activation of the kinase. This specific compartmentalization mechanism occurs through high-affinity interactions of PKA with A-kinase anchoring proteins (AKAPs), the role of which is to target the kinase to discrete subcellular microdomains. Recently, a peptide designated "AKAPis" has been proposed to competitively inhibit PKA-AKAP interactions in vitro. We therefore sought to characterize a cell-permeable construct of the AKAPis inhibitor and use it as a tool to characterize the impact of PKA compartmentalization by AKAPs. Using insulin-secreting pancreatic beta-cells (INS-1 cells), we showed that TAT-AKAPis (at a micromolar range) dose dependently disrupted a significant fraction of endogenous PKA-AKAP interactions. Immunoflurescent analysis also indicated that TAT-AKAPis significantly affected PKA subcellular localization. Furthermore, TAT-AKAPis markedly attenuated glucagon-induced phosphorylations of p44/p42 MAPKs and cAMP response element binding protein, which are downstream effectors of PKA. In parallel, TAT-AKAPis dose dependently inhibited the glucagon-induced potentiation of insulin release. Therefore, AKAP-mediated subcellular compartmentalization of PKA represents a key mechanism for PKA-dependent phosphorylation events and potentiation of insulin secretion in intact pancreatic beta-cells. More interestingly, our data highlight the effectiveness of the cell-permeable peptide-mediated approach to monitoring in cellulo PKA-AKAP interactions and delineating PKA-dependent phosphorylation events underlying specific cellular responses."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00216.2008"xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Petit P."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Bataille D."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Le-Nguyen D."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Hani E.H."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Lajoix A.D."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Faruque O.M."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/author | "Vives E."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/pages | "C306-16"xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/title | "Cell-permeable peptide-based disruption of endogenous PKA-AKAP complexes: a tool for studying the molecular roles of AKAP-mediated PKA subcellular anchoring."xsd:string |
http://purl.uniprot.org/citations/19073898 | http://purl.uniprot.org/core/volume | "296"xsd:string |
http://purl.uniprot.org/citations/19073898 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19073898 |
http://purl.uniprot.org/citations/19073898 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19073898 |
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http://purl.uniprot.org/uniprot/#_P22612-mappedCitation-19073898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19073898 |
http://purl.uniprot.org/uniprot/#_P22694-mappedCitation-19073898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19073898 |
http://purl.uniprot.org/uniprot/#_P31321-mappedCitation-19073898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19073898 |