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http://purl.uniprot.org/citations/17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17698854http://www.w3.org/2000/01/rdf-schema#comment"P-Rex1 is a guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that is directly activated by the betagamma subunits of heterotrimeric G proteins and by the lipid second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)), which is generated by phosphoinositide 3-kinase (PI3K). Gbetagamma subunits and PIP(3) are membrane-bound, whereas the intracellular localization of P-Rex1 in basal cells is cytosolic. Activation of PI3K alone is not sufficient to promote significant membrane translocation of P-Rex1. Here we investigated the subcellular localization of P-Rex1 by fractionation of Sf9 cells co-expressing P-Rex1 with Gbetagamma and/or PI3K. In basal, serum-starved cells, P-Rex1 was mainly cytosolic, but 7% of the total was present in the 117,000 x g membrane fraction. Co-expression of P-Rex1 with either Gbetagamma or PI3K caused only an insignificant increase in P-Rex1 membrane localization, whereas Gbetagamma and PI3K together synergistically caused a robust increase in membrane-localized P-Rex1 to 23% of the total. PI3K-driven P-Rex1 membrane recruitment was wortmannin-sensitive. The use of P-Rex1 mutants showed that the isolated Dbl homology/pleckstrin homology domain tandem of P-Rex1 is sufficient for synergistic Gbetagamma- and PI3K-driven membrane localization; that the enzymatic GEF activity of P-Rex1 is not required for membrane translocation; and that the other domains of P-Rex1 (DEP, PDZ, and IP4P) contribute to keeping the enzyme localized in the cytosol of basal cells. In vitro Rac2-GEF activity assays showed that membrane-derived purified P-Rex1 has a higher basal activity than cytosol-derived P-Rex1, but both can be further activated by PIP(3) and Gbetagamma subunits."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m701877200"xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Thelen M."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Donald S."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Anderson K.E."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Thelen S."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Welch H.C."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/author"Barber M.A."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/pages"29967-29976"xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/title"Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase."xsd:string
http://purl.uniprot.org/citations/17698854http://purl.uniprot.org/core/volume"282"xsd:string
http://purl.uniprot.org/citations/17698854http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17698854
http://purl.uniprot.org/citations/17698854http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17698854
http://purl.uniprot.org/uniprot/#_P52735-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_Q14185-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_A0A2X0SFH1-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_Q12979-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_Q13009-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_O75962-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_P15498-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_P10911-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854
http://purl.uniprot.org/uniprot/#_Q8IZD9-mappedCitation-17698854http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17698854