AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho transduction pathways
Détails
ID Serval
serval:BIB_2925678259BD
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho transduction pathways
Périodique
European Journal of Cell Biology
ISSN
0171-9335 (Print)
Statut éditorial
Publié
Date de publication
07/2006
Volume
85
Numéro
7
Pages
603-10
Notes
Journal Article
Review --- Old month value: Jul
Review --- Old month value: Jul
Résumé
A Kinase-anchoring proteins (AKAPs) are a family of functionally related proteins involved in the targeting of the PKA holoenzyme towards specific physiological substrates. We have recently identified a novel anchoring protein expressed in cardiomyocytes, called AKAP-Lbc, that functions as a PKA-targeting protein as well as a guanine nucleotide exchange factor (GEF) that activates the GTPase RhoA. Here, we discuss the most recent findings elucidating the molecular mechanisms and the transduction pathways involved in the regulation of the AKAP-Lbc signaling complex inside cells. We could show that AKAP-Lbc is regulated in a bi-directional manner by signals that activate or deactivate its Rho-GEF activity. Activation of AKAP-Lbc occurs in response to agonists that stimulate G proteins coupled receptors linked to the heterotrimeric G protein G12, whereas inactivation occurs through mechanisms that require phosphorylation of AKAP-Lbc by anchored PKA and subsequent recruitment of the regulatory protein 14-3-3. Interestingly, we could demonstrate that AKAP-Lbc can form homo-oligomers inside cells and that 14-3-3 can inhibit the Rho-GEF activity of AKAP-Lbc only when the anchoring protein adopts an oligomeric conformation. These findings reveal the molecular architecture of the AKAP-Lbc transduction complex and provide a mechanistic explanation of how upstream signaling pathways can be integrated within the AKAP-Lbc transduction complex to precisely modulate the activation of Rho.
Mots-clé
14-3-3 Proteins/metabolism
Adaptor Proteins, Signal Transducing/*physiology
Cyclic AMP/*metabolism
Cyclic AMP-Dependent Protein Kinases/metabolism
Humans
Models, Biological
Multiprotein Complexes
Myocytes, Cardiac/metabolism
Polymers/metabolism
*Signal Transduction
rho GTP-Binding Proteins/*metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 13:14
Dernière modification de la notice
20/08/2019 14:08