| First Author | Perino A | Year | 2011 |
| Journal | Mol Cell | Volume | 42 |
| Issue | 1 | Pages | 84-95 |
| PubMed ID | 21474070 | Mgi Jnum | J:172667 |
| Mgi Id | MGI:5008515 | Doi | 10.1016/j.molcel.2011.01.030 |
| Citation | Perino A, et al. (2011) Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110gamma. Mol Cell 42(1):84-95 |
| abstractText | Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110gamma participates in these processes by sustaining beta-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110gamma anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110gamma to inhibit PIP(3) production. This provides local feedback control of PIP(3) and cAMP signaling events. In congestive heart failure, p110gamma is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in beta-adrenergic receptor density. Pharmacological inhibition of p110gamma normalizes beta-adrenergic receptor density and improves contractility in failing hearts. |
