@article{197ecdaab0d747a4b13700cfe2023106,
title = "Integrating Cardiac PIP3 and cAMP Signaling through a PKA Anchoring Function of p110γ",
abstract = "Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110γ participates in these processes by sustaining β-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110γ anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110γ to inhibit PIP3 production. This provides local feedback control of PIP3 and cAMP signaling events. In congestive heart failure, p110γ is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in β-adrenergic receptor density. Pharmacological inhibition of p110γ normalizes β-adrenergic receptor density and improves contractility in failing hearts.",
author = "Alessia Perino and Alessandra Ghigo and Enrico Ferrero and Fulvio Morello and Gaetano Santulli and Baillie, {George S.} and Federico Damilano and Dunlop, {Allan J.} and Catherine Pawson and Romy Walser and Renzo Levi and Fiorella Altruda and Lorenzo Silengo and Langeberg, {Lorene K.} and Gitte Neubauer and Stephane Heymans and Giuseppe Lembo and Wymann, {Matthias P.} and Reinhard Wetzker and Houslay, {Miles D.} and Guido Iaccarino and Scott, {John D.} and Emilio Hirsch",
note = "Funding Information: We would like to thank M. Zaccolo (University of Glasgow), J. Beavo (University of Washington), J. Hamm (University of Torino), and all the members of E.H.'s lab. This work was supported by grants from Fondation Leducq (06CDV02 to E.H., J.D.S., G.S.B., and M.D.H.), the European Union Sixth Framework Program EuGeneHeart (E.H.), Telethon (E.H.), Regione Piemonte (E.H.), University of Torino (E.H.), AIRC (E.H.), NIH (grant HL08836 to J.D.S.), and Medical Research Council UK (G0600675 to G.S.B. and M.D.H.). ",
year = "2011",
month = apr,
day = "8",
doi = "10.1016/j.molcel.2011.01.030",
language = "English (US)",
volume = "42",
pages = "84--95",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}