Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase γ that is highly expressed in heart and interacts with PDE3B

Abstract

Phosphoinositide 3-kinase (PI3K) γ has been implicated in a vast array of physiological settings including the activation of different leukocyte species and the regulation of myocardial contractility. Activation of PI3Kγ is primarily mediated by Gβγ subunits of heterotrimeric G proteins, which are recognized by a p101 regulatory subunit. Here, we describe the identification and characterization of a novel regulatory subunit of PI3Kγ, which we termed p87PIKAP (PI3Kγ adapter protein of 87 kDa). It is homologous to p101 in areas that we have recently shown that they mediate binding to the catalytic p110γ subunit and to Gβγ. Like p101, p87PIKAP binds to both p110γ and Gβγ and mediates activation of p110γ downstream of G protein-coupled receptors. In contrast to p101, p87PIKAP is highly expressed in heart and may therefore be crucial to PI3Kγ cardiac function. Moreover, p87 PIKAP and p101 are both expressed in dendritic cells, macrophages, and neutrophils, raising the possibility of regulatory subunit-dependent differences in PI3Kγ signaling within the same cell type. We further provide evidence that p87PIKAP physically interacts with phosphodiesterase (PDE) 3B, suggesting that p87PIKAP is also involved in the recently described noncatalytic scaffolding interaction of p110γ with PDE3B. However, coexpression of PDE3B and PI3Kγ subunits was not sufficient to reconstitute the regulatory effect of PI3Kγ on PDE3B activity observed in heart, implying further molecules to be present in the complex regulating PDE3B in heart. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.