Gβγ is a direct regulator of endogenous p101/p110γ and p84/p110γ PI3Kγ complexes in mouse neutrophils
Natalie K. Rynkiewicz, Karen E. Anderson, Sabine Suire, D.M. Collins, Eleftherios Karanasios, Oscar Vadas, Roger Williams, David Oxley, Jonathan Clark, Len Stephens, Phillip T. Hawkins
Abstract
MLP and C5a, suggesting that competition may exist between p101/p110γ and p84/p110γ for Gβγ subunits downstream of GPCR activation. GPCRs did not activate p110γ in neutrophils from mice lacking both the p101 and p84 regulatory subunits, indicating that RAS binding to p110γ is insufficient to support GPCR activation in this cell type. These findings define a direct role for Gβγ subunits in activating both of the endogenous PI3Kγ complexes and indicate that the regulatory PI3Kγ subunit biases activation toward different GPCRs.
Topics & Concepts
RegulatorEndogenyChemistryCell biologyImmunologyBiologyBiochemistryGeneProtein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerProtein Tyrosine Phosphatases