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http://purl.uniprot.org/citations/17398097http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17398097http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17398097http://www.w3.org/2000/01/rdf-schema#comment"The GTPase Arf6 regulates multiple cellular processes, including endocytosis, secretion, phagocytosis, cell adhesion, and cell migration [1, 2]. The Arf6-specific GAP ACAP1 is a negative regulator of Arf6-mediated signaling [3-7]. However, regulation of ACAP1- and Arf6-mediated signaling by other cellular proteins is not well understood. GULP/CED-6 is a phosphotyrosine binding (PTB)-domain-containing adaptor protein linked to engulfment of apoptotic cells [8-13] and to cholesterol homeostasis [14]. Here, we identify a novel role for GULP as a positive regulator of Arf6. Knockdown of GULP decreased cellular Arf6-GTP, whereas GULP overexpression increased cellular Arf6-GTP. At the mechanistic level, GULP influenced Arf6 at four levels. First, GULP bound directly to GDP-bound Arf6 via its PTB domain. Second, GULP associated with the Arf6-GAP ACAP1 at endogenous levels. Third, GULP reversed the Arf6-GTP decrease induced by ACAP1, and countered the ACAP1-mediated inhibition of cell migration. Fourth, GULP, ACAP1, and GDP-bound Arf6 were part of a tripartite complex, suggesting sequestration of ACAP1 as one mechanism of GULP action. Taken together, these data identify GULP as a modifier of cellular Arf6-GTP through regulation of ACAP1. Because PTB-domain-containing adaptor proteins influence endocytosis and trafficking of membrane proteins and cell migration [15, 16], our data support a model wherein PTB-domain-containing adaptor proteins regulate Arf family proteins."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.org/dc/terms/identifier"doi:10.1016/j.cub.2007.03.014"xsd:string
http://purl.uniprot.org/citations/17398097http://purl.org/dc/terms/identifier"doi:10.1016/j.cub.2007.03.014"xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Ma Z."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Ma Z."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Luo R."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Luo R."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Casanova J.E."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Casanova J.E."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Nie Z."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Nie Z."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Ravichandran K.S."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/author"Ravichandran K.S."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/pages"722-727"xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/pages"722-727"xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/title"Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/title"Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP."xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/volume"17"xsd:string
http://purl.uniprot.org/citations/17398097http://purl.uniprot.org/core/volume"17"xsd:string