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http://purl.uniprot.org/citations/19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19073898http://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/19073898http://purl.org/dc/terms/identifier"doi:10.1152/ajpcell.00216.2008"xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Petit P."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Bataille D."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Le-Nguyen D."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Hani E.H."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Lajoix A.D."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Faruque O.M."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/author"Vives E."xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/name"Am J Physiol Cell Physiol"xsd:string
http://purl.uniprot.org/citations/19073898http://purl.uniprot.org/core/pages"C306-16"xsd:string
http://purl.uniprot.org/citations/19073898http://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/19073898http://purl.uniprot.org/core/volume"296"xsd:string
http://purl.uniprot.org/citations/19073898http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19073898
http://purl.uniprot.org/citations/19073898http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19073898
http://purl.uniprot.org/uniprot/#_P13861-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P24588-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P46940-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P10644-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P17612-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P22612-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P22694-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898
http://purl.uniprot.org/uniprot/#_P31321-mappedCitation-19073898http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19073898