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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Differential Regulation of Lipid and Protein Kinase Activities of Phosphoinositide 3-Kinase γ in Vitro

Andrey Bondev / Ignacio Rubio / Reinhard Wetzker

Citation Information: Biological Chemistry. Volume 380, Issue 11, Pages 1337–1340, ISSN (Print) 1431-6730, DOI: 10.1515/BC.1999.171, June 2005

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G protein sensitive phosphoinositide 3-kinase γ(PI3Kγ) has been characterised as a pleiotropic signalling protein expressing lipid kinase and protein kinase activities. Whereas the regulation of the lipid kinase activity has been investigated in detail, the regulatory features of PI3Kγ protein kinase activity are unknown. Here we report that Gβγ subunits of heterotrimeric G proteins induce a biphasic response of PI3Kγ autophosphorylation in vitro, which contrasts the regulatory effects of the G proteins on PI3Kγ lipid kinase activity. In addition to autophosphorylation PI3Kγ is able to catalyse transphosphorylation of the adapter protein p101 and the protein kinase MEK-1. In the presence of the p101, Gβγ affects PI3Kγ protein kinase activities in a complex manner. In summary, the differential regulatory effects of heterotrimeric G proteins on PI3Kγ lipid and protein kinase activities in vitro reflect the functional diversity of the enzyme observed in vivo.

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