| http://purl.uniprot.org/citations/22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22378744 | http://www.w3.org/2000/01/rdf-schema#comment | "The cAMP/PKA signaling system constitutes an inhibitory pathway in T cells and, although its biochemistry has been thoroughly investigated, its possible effects on ion channels are still not fully understood. K(V)1.3 channels play an important role in T-cell activation, and their inhibition suppresses T-cell function. It has been reported that PKA modulates K(V)1.3 activity. Two PKA isoforms are expressed in human T cells: PKAI and PKAII. PKAI has been shown to inhibit T-cell activation via suppression of the tyrosine kinase Lck. The aim of this study was to determine the PKA isoform modulating K(V)1.3 and the signaling pathway underneath. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a nonselective activator of PKA, inhibited K(V)1.3 currents both in primary human T and in Jurkat cells. This inhibition was prevented by the PKA blocker PKI(6-22). Selective knockdown of PKAI, but not PKAII, with siRNAs abolished the response to 8-BrcAMP. Additional studies were performed to determine the signaling pathway mediating PKAI effect on K(V)1.3. Overexpression of a constitutively active mutant of Lck reduced the response of K(V)1.3 to 8-Br-cAMP. Moreover, knockdown of the scaffolding protein disc large 1 (Dlg1), which binds K(V)1.3 to Lck, abolished PKA modulation of K(V)1.3 channels. Immunohistochemistry studies showed that PKAI, but not PKAII, colocalizes with K(V)1.3 and Dlg1 indicating a close proximity between these proteins. These results indicate that PKAI selectively regulates K(V)1.3 channels in human T lymphocytes. This effect is mediated by Lck and Dlg1. We thus propose that the K(V)1.3/Dlg1/Lck complex is part of the membrane pathway that cAMP utilizes to regulate T-cell function."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00263.2011"xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Kucher V."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Conforti L."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Gordon S.M."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Neumeier L."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Filipovich A.H."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Chimote A.A."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/author | "Kuras Z."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/pages | "C1504-12"xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/title | "Modulation of Kv1.3 channels by protein kinase A I in T lymphocytes is mediated by the disc large 1-tyrosine kinase Lck complex."xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://purl.uniprot.org/core/volume | "302"xsd:string |
| http://purl.uniprot.org/citations/22378744 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22378744 |
| http://purl.uniprot.org/citations/22378744 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22378744 |
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| http://purl.uniprot.org/uniprot/#_A0A3G9CMV0-mappedCitation-22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22378744 |
| http://purl.uniprot.org/uniprot/#_A0A3G9CMW0-mappedCitation-22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22378744 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DFT3-mappedCitation-22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22378744 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3T3-mappedCitation-22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22378744 |
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| http://purl.uniprot.org/uniprot/#_B4DF78-mappedCitation-22378744 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22378744 |