A-Kinase Anchoring Protein (AKAP)-Lbc Anchors a PKN-based Signaling Complex Involved in α1-Adrenergic Receptor-induced p38 Activation.

Détails

ID Serval
serval:BIB_8A6E2F2885F8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A-Kinase Anchoring Protein (AKAP)-Lbc Anchors a PKN-based Signaling Complex Involved in α1-Adrenergic Receptor-induced p38 Activation.
Périodique
Journal of Biological Chemistry
Auteur(s)
Cariolato Luca, Cavin Sabrina, Diviani Dario
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2011
Volume
286
Numéro
10
Pages
7925-7937
Langue
anglais
Résumé
The mitogen-activated protein kinases (MAPKs) pathways are highly organized signaling systems that transduce extracellular signals into a variety of intracellular responses. In this context, it is currently poorly understood how kinases constituting these signaling cascades are assembled and activated in response to receptor stimulation to generate specific cellular responses. Here, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critically involved in the activation of the p38α MAPK downstream of α(1b)-adrenergic receptors (α(1b)-ARs). Our results indicate that AKAP-Lbc can assemble a novel transduction complex containing the RhoA effector PKNα, MLTK, MKK3, and p38α, which integrates signals from α(1b)-ARs to promote RhoA-dependent activation of p38α. In particular, silencing of AKAP-Lbc expression or disrupting the formation of the AKAP-Lbc·p38α signaling complex specifically reduces α(1)-AR-mediated p38α activation without affecting receptor-mediated activation of other MAPK pathways. These findings provide a novel mechanistic hypothesis explaining how assembly of macromolecular complexes can specify MAPK signaling downstream of α(1)-ARs.
Mots-clé
nucleotide exchange factors, cardiac-hypertrophy, dbl family, rho, scaffold, pathways, phosphorylation, expression, induction, apoptosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/03/2011 14:37
Dernière modification de la notice
20/10/2020 11:12
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