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Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ

Perino, A. and Ghigo, A. and Ferrero, E. and Morello, F. and Santulli, G. and Baillie, G. S. and Damilano, F. and Dunlop, A. J. and Pawson, C. and Walser, R. and Levi, R. and Altruda, F. and Silengo, L. and Langeberg, L. K. and Neubauer, G. and Heymans, S. and Lembo, G. and Wymann, M. P. and Wetzker, R. and Houslay, M. D. and Iaccarino, G. and Scott, J. D. and Hirsch, E.. (2011) Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ. Molecular cell, Vol. 42, H. 1. pp. 84-95.

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Official URL: http://edoc.unibas.ch/dok/A6004145

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Abstract

Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110? participates in these processes by sustaining ?-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110? anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110? to inhibit PIP(3) production. This provides local feedback control of PIP(3) and cAMP signaling events. In congestive heart failure, p110? is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in ?-adrenergic receptor density. Pharmacological inhibition of p110? normalizes ?-adrenergic receptor density and improves contractility in failing hearts.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)
UniBasel Contributors:Wymann, Matthias P.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1097-2765
Note:Variant title: Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110gamma -- Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:27 Mar 2014 13:13

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