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http://purl.uniprot.org/citations/18625701http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18625701http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18625701http://www.w3.org/2000/01/rdf-schema#comment"The 55-kDa TNFR1 (type I tumor necrosis factor receptor) can be released to the extracellular space by two mechanisms, the proteolytic cleavage and shedding of soluble receptor ectodomains and the release of full-length receptors within exosome-like vesicles. We have shown that the brefeldin A-inhibited guanine nucleotide exchange protein BIG2 associates with TNFR1 and selectively modulates the release of TNFR1 exosome-like vesicles via an ARF1- and ARF3-dependent mechanism. Here, we assessed the role of BIG2 A kinase-anchoring protein (AKAP) domains in the regulation of TNFR1 exosome-like vesicle release from human vascular endothelial cells. We show that 8-bromo-cyclic AMP induced the release of full-length, 55-kDa TNFR1 within exosome-like vesicles via a protein kinase A (PKA)-dependent mechanism. Using RNA interference to decrease specifically the levels of individual PKA regulatory subunits, we demonstrate that RIIbeta modulates both the constitutive and cAMP-induced release of TNFR1 exosome-like vesicles. Consistent with its AKAP function, BIG2 was required for the cAMP-induced PKA-dependent release of TNFR1 exosome-like vesicles via a mechanism that involved the binding of RIIbeta to BIG2 AKAP domains B and C. We conclude that both the constitutive and cAMP-induced release of TNFR1 exosome-like vesicles occur via PKA-dependent pathways that are regulated by the anchoring of RIIbeta to BIG2 via AKAP domains B and C. Thus, BIG2 regulates TNFR1 exosome-like vesicle release by two distinct mechanisms, as a guanine nucleotide exchange protein that activates class I ADP-ribosylation factors and as an AKAP for RIIbeta that localizes PKA signaling within cellular TNFR1 trafficking pathways."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m804966200"xsd:string
http://purl.uniprot.org/citations/18625701http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m804966200"xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Lam J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Lam J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Moss J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Moss J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Vaughan M."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Vaughan M."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Jones H."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Jones H."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Islam A."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Islam A."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Hiroi T."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Hiroi T."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Levine S.J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/author"Levine S.J."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/18625701http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string