Chatting Second Messengers: PIP3 and cAMP

  • Alessandra Ghigo
  • Flora Pirozzi
  • Mingchuan Li
  • Emilio HirschEmail author
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 3)


3′-5′-cyclic adenosine monophosphate (cAMP) and phosphatidylinositol 3,4,5 trisphosphate (PIP3) are pleiotropic second messengers generated in response to activation of G protein-coupled receptors (GPCRs) by a wide array of hormones and neurotransmitters. Although these small molecules engage distinct and seemingly unrelated downstream signal transducers, a growing body of evidence points to a strict cooperation of cAMP and PIP3 cascades in the control of cardiomyocyte functions. Dynamic macromolecular complexes of cAMP and PIP3 molecular switches assemble into spatially and temporally restricted microdomains. Deciphering how these compartmentalized complexes form and affect the interactions between the two signaling systems is of crucial importance, since both pathways are severely deregulated in major cardiac diseases, such as heart failure. This chapter summarizes recently described mechanisms governing the bidirectional cross talk between cAMP and PIP3 signaling pathways in the pathophysiological control of cardiovascular function. In particular, we will describe how membrane-located PIP3 affects both initiation and termination of cAMP signaling as well as the negative feedback loop whereby the small and diffusible intracellular messenger, cAMP, influences PIP3 production.


Cyclic AMP Protein kinase A Phosphatidylinositol 3,4,5 trisphosphate Protein kinase B β-Adrenergic receptor Phosphodiesterase Heart failure 


Compliance with Ethical Standards

Conflict of Interest Statement

Emilio Hirsch is cofounder of Kither Biotech, a company involved in the development of PI3K inhibitors. The other authors declare no conflict of interest.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Alessandra Ghigo
    • 1
  • Flora Pirozzi
    • 2
  • Mingchuan Li
    • 1
  • Emilio Hirsch
    • 1
    Email author
  1. 1.Department of Molecular Biotechnology and Health SciencesUniversity of TorinoTorinoItaly
  2. 2.Division of Internal Medicine, Department of Translational Medical SciencesFederico II UniversityNaplesItaly

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