title: The p101 subunit of PI3Kγ restores activation by Gβ mutants deficient in stimulating p110γ.
abstract: G-protein-regulated PI3Kγ (phosphoinositide 3-kinase γ) plays a crucial role in inflammatory and allergic processes. PI3Kγ, a dimeric protein formed by the non-catalytic p101 and catalytic p110γ subunits, is stimulated by receptor-released Gβγ complexes. We have demonstrated previously that Gβγ stimulates both monomeric p110γ and dimeric p110γ/p101 lipid kinase activity in vitro. In order to identify the Gβ residues responsible for the Gβγ-PI3Kγ interaction, we examined Gβ1 mutants for their ability to stimulate lipid and protein kinase activities and to recruit PI3Kγ to lipid vesicles. Our findings revealed different interaction profiles of Gβ residues interacting with p110γ or p110γ/p101. Moreover, p101 was able to rescue the stimulatory activity of Gβ1 mutants incapable of modulating monomeric p110γ. In addition to the known adaptor function of p101, in the present paper we show a novel regulatory role of p101 in the activation of PI3Kγ.
authors: Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Centre of Pharmacogenomics and Pharmaceutical Research, University of Tübingen, 72074 Tübingen, Germany.
authors: Aliaksei
authors: A
authors: Shymanets
authors: Mohammad R
authors: MR
authors: Ahmadian
authors: Katja T
authors: KT
authors: Kössmeier
authors: Reinhard
authors: R
authors: Wetzker
authors: Christian
authors: C
authors: Harteneck
authors: Bernd
authors: B
authors: Nürnberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D018411:Spodoptera; D014162:Transfection; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D044387:GTP-Binding Protein beta Subunits; D007527:Isoenzymes; D050505:Mutant Proteins; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse; D014357:Trypsin