Related Experiment Video

Updated: Aug 7, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Identification of the macromolecular complex responsible for PI3Kgamma-dependent regulation of cAMP levels

A Perino1, A Ghigo, F Damilano

  • 1Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5bis, 10126 Torino, Italy. alessia.perino@libero.it

Biochemical Society Transactions
|July 22, 2006
PubMed

Insights

Phosphoinositide 3-kinase gamma (PI3Kgamma) regulates cardiac contractility via a kinase-independent mechanism involving cAMP levels. PI3Kgamma forms a complex with PDE3B, influencing cardiac function and cAMP homeostasis.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphoinositide 3-kinase gamma (PI3Kgamma) is known for its lipid and protein kinase activities, primarily in leukocytes.
  • Recent studies reveal PI3Kgamma's presence and role in cardiac function regulation.
  • PI3Kgamma acts as a negative modulator of cardiac contractility by affecting cyclic adenosine monophosphate (cAMP) levels.

Purpose of the Study:

  • To investigate the mechanism by which PI3Kgamma influences cardiac contractility.
  • To determine if PI3Kgamma's kinase activity is essential for its cardiac function.
  • To elucidate the role of PI3Kgamma in cardiac cAMP homeostasis.

Main Methods:

  • Comparison of PI3Kgamma-deficient mice with wild-type controls.
  • Analysis of cAMP levels in knock-in mouse mutants expressing a kinase-dead PI3Kgamma.
  • Investigation of PI3Kgamma's interaction with phosphodiesterase 3B (PDE3B) in a macromolecular complex.

Main Results:

  • PI3Kgamma-deficient mice exhibit elevated cAMP levels, indicating a role in cAMP regulation.
  • Kinase-dead PI3Kgamma mutants show normal cAMP levels, suggesting a kinase-independent mechanism.
  • PI3Kgamma forms a complex with PDE3B, a key enzyme in cAMP degradation.

Conclusions:

  • PI3Kgamma regulates cardiac cAMP homeostasis through a kinase-independent mechanism.
  • PI3Kgamma's interaction with PDE3B is crucial for modulating cardiac contractility.
  • The PI3Kgamma-PDE3B complex may be regulated by protein kinase A, impacting cardiac function.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...