Characterization of P87Pikap, a novel regulatory subunit of phosphoinositide 3-kinase gamma  that is highly expressed in heart and interacts with PDE3B

doi:10.1074/jbc.M512502200

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Papers In Press, published online ahead of print February 13, 2006
J. Biol. Chem, 10.1074/jbc.M512502200
Submitted on November 22, 2005
Revised on February 8, 2006
Accepted on February 13, 2006

Characterization of P87Pikap, a novel regulatory subunit of phosphoinositide 3-kinase $gamma$ that is highly expressed in heart and interacts with PDE3B

Philipp Voigt, Martin B. Dorner, and Michael Schaefer

Institut für Pharmakologie, Charité - Universitätsmedizin Berlin, Berlin, Berlin 14195

Corresponding Author: schae{at}zedat.fu-berlin.de

Phosphoinositide 3-kinase (PI3K) $gamma$ 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 PI3K $gamma$ is primarily mediated by G $beta$ $gamma$ 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 PI3K $gamma$ , which we termed p87^PIKAP (PI3K $gamma$ adapter protein of 87 kDa). It is homologous to p101 in areas of which we have recently shown that they mediate binding to the catalytic p110 $gamma$ subunit and to G $beta$ $gamma$ . Like p101, p87^PIKAP binds to both p110 $gamma$ and G $beta$ $gamma$ and mediates activation of p110 $gamma$ downstream of G-protein-coupled receptors. In contrast to p101, p87^PIKAP is highly expressed in heart and may therefore be crucial to PI3K $gamma$ 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 PI3K $gamma$ signaling within the same cell type. We further provide evidence that p87^PIKAP physically interacts with phosphodiesterase (PDE) 3B, suggesting that also p87^PIKAP is involved in the recently described non-catalytic scaffolding interaction of p110 $gamma$ with PDE3B. However, coexpression of PDE3B and PI3K $gamma$ subunits was not sufficient to reconstitute the regulatory effect of PI3K $gamma$ on PDE3B activity observed in heart, implying further molecules to be present in the complex regulating PDE3B in heart.

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Characterization of P87Pikap, a novel regulatory subunit of phosphoinositide 3-kinase that is highly expressed in heart and interacts with PDE3B

Characterization of P87Pikap, a novel regulatory subunit of phosphoinositide 3-kinase $gamma$ that is highly expressed in heart and interacts with PDE3B