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.
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February 2012
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Research Article|
January 16 2012
The p101 subunit of PI3Kγ restores activation by Gβ mutants deficient in stimulating p110γ
Aliaksei Shymanets;
Aliaksei Shymanets
*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
†Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany
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Mohammad R. Ahmadian;
Mohammad R. Ahmadian
†Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany
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Katja T. Kössmeier;
Katja T. Kössmeier
†Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany
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Reinhard Wetzker;
Reinhard Wetzker
‡Department of Molecular Cell Biology, Centre for Molecular Biomedicine, Jena University Hospital, 07745 Jena, Germany
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Christian Harteneck;
Christian Harteneck
*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
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Bernd Nürnberg
Bernd Nürnberg
1
*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
†Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany
1To whom correspondence should be addressed (email bernd.nuernberg@uni-tuebingen.de).
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Publisher: Portland Press Ltd
Received:
September 14 2011
Revision Received:
November 04 2011
Accepted:
November 07 2011
Accepted Manuscript online:
November 07 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (3): 851–858.
Article history
Received:
September 14 2011
Revision Received:
November 04 2011
Accepted:
November 07 2011
Accepted Manuscript online:
November 07 2011
Citation
Aliaksei Shymanets, Mohammad R. Ahmadian, Katja T. Kössmeier, Reinhard Wetzker, Christian Harteneck, Bernd Nürnberg; The p101 subunit of PI3Kγ restores activation by Gβ mutants deficient in stimulating p110γ. Biochem J 1 February 2012; 441 (3): 851–858. doi: https://doi.org/10.1042/BJ20111664
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