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http://purl.uniprot.org/citations/12507995http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12507995http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12507995http://www.w3.org/2000/01/rdf-schema#comment"Receptor-regulated class I phosphoinositide 3-kinases (PI3K) phosphorylate the membrane lipid phosphatidylinositol (PtdIns)-4,5-P2 to PtdIns-3,4,5-P3. This, in turn, recruits and activates cytosolic effectors with PtdIns-3,4,5-P3-binding pleckstrin homology (PH) domains, thereby controlling important cellular functions such as proliferation, survival, or chemotaxis. The class IB p110 gamma/p101 PI3K gamma is activated by G beta gamma on stimulation of G protein-coupled receptors. It is currently unknown whether in living cells G beta gamma acts as a membrane anchor or an allosteric activator of PI3K gamma, and which role its noncatalytic p101 subunit plays in its activation by G beta gamma. Using GFP-tagged PI3K gamma subunits expressed in HEK cells, we show that G beta gamma recruits the enzyme from the cytosol to the membrane by interaction with its p101 subunit. Accordingly, p101 was found to be required for G protein-mediated activation of PI3K gamma in living cells, as assessed by use of GFP-tagged PtdIns-3,4,5-P3-binding PH domains. Furthermore, membrane-targeted p110 gamma displayed basal enzymatic activity, but was further stimulated by G beta gamma, even in the absence of p101. Therefore, we conclude that in vivo, G beta gamma activates PI3K gamma by a mechanism assigning specific roles for both PI3K gamma subunits, i.e., membrane recruitment is mediated via the noncatalytic p101 subunit, and direct stimulation of G beta gamma with p110 gamma contributes to activation of PI3K gamma."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.org/dc/terms/identifier"doi:10.1083/jcb.200210115"xsd:string
http://purl.uniprot.org/citations/12507995http://purl.org/dc/terms/identifier"doi:10.1083/jcb.200210115"xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Schaefer M."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Schaefer M."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Czupalla C."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Czupalla C."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Schultz G."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Schultz G."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Nurnberg B."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Nurnberg B."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Brock C."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Brock C."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Michalke M."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Michalke M."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Reusch H.P."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Reusch H.P."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Spicher K."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/author"Spicher K."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/name"J. Cell Biol."xsd:string
http://purl.uniprot.org/citations/12507995http://purl.uniprot.org/core/name"J. Cell Biol."xsd:string