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Assigning Functional Domains within the p101 Regulatory Subunit of Phosphoinositide 3-Kinase γ

Philipp Voigt, Carsten Brock, Bernd Nürnberg, Michael Schaefer
2004 Journal of Biological Chemistry  
Phosphoinositide 3-Kinase (PI3K) ␥ is a lipid kinase that is regulated by G-protein-coupled receptors. It plays a crucial role in inflammatory and allergic processes. Activation of PI3K␥ is primarily mediated by G␤␥ subunits. The regulatory p101 subunit of PI3K␥ binds to G␤␥ and, thereby, recruits the catalytic p110␥ subunit to the plasma membrane. Despite its crucial role in the activation of PI3K␥, the structural organization of p101 is still largely elusive. Employing fluorescence resonance
more » ... rescence resonance energy transfer measurements, coimmunoprecipitation and colocalization studies with p101 deletion mutants, we show here that distinct regions within the p101 primary structure are responsible for interaction with p110␥ and G␤␥. The p110␥ binding site is confined to the N terminus, whereas binding to G␤␥ is mediated by a C-terminal domain of p101. These domains appear to be highly conserved among various species ranging from Xenopus to men. In addition to establishing a domain structure for p101, our results point to the existence of a previously unknown, p101-related regulatory subunit for PI3K␥.
doi:10.1074/jbc.m413104200 pmid:15611065 fatcat:scni2qthrff3zlgyvubmm4tvge