RGD Reference Report - Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins. - Rat Genome Database

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Pathways

Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins.

Authors: Ceccarini, Marina  Grasso, Margherita  Veroni, Caterina  Gambara, Guido  Artegiani, Benedetta  Macchia, Gianfranco  Ramoni, Carlo  Torreri, Paola  Mallozzi, Cinzia  Petrucci, Tamara C  Macioce, Pompeo 
Citation: Ceccarini M, etal., J Mol Biol. 2007 Aug 31;371(5):1174-87. doi: 10.1016/j.jmb.2007.06.019. Epub 2007 Jun 14.
RGD ID: 126781731
Pubmed: PMID:17610895   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jmb.2007.06.019   (Journal Full-text)

The dystrophin-related and -associated protein dystrobrevin is a component of the dystrophin-associated protein complex, which directly links the cytoskeleton to the extracellular matrix. It is now thought that this complex also serves as a dynamic scaffold for signaling proteins, and dystrobrevin may play a role in this context. Since dystrobrevin involvement in signaling pathways seems to be dependent on its interaction with other proteins, we sought new insights and performed a two-hybrid screen of a mouse brain cDNA library using beta-dystrobrevin, the isoform expressed in non-muscle tissues, as bait. Among the positive clones characterized after the screen, one encodes the regulatory subunit RIalpha of the cAMP-dependent protein kinase A (PKA). We confirmed the interaction by in vitro and in vivo association assays, and mapped the binding site of beta-dystrobrevin on RIalpha to the amino-terminal region encompassing the dimerization/docking domain of PKA regulatory subunit. We also found that the domain of interaction for RIalpha is contained in the amino-terminal region of beta-dystrobrevin. We obtained evidence that beta-dystrobrevin also interacts directly with RIIbeta, and that not only beta-dystrobrevin but also alpha-dystrobrevin interacts with PKA regulatory subunits. We show that both alpha and beta-dystrobrevin are specific phosphorylation substrates for PKA and that protein phosphatase 2A (PP2A) is associated with dystrobrevins. Our results suggest a new role for dystrobrevin as a scaffold protein that may play a role in different cellular processes involving PKA signaling.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Dtna  (dystrobrevin, alpha)
Dtnb  (dystrobrevin, beta)
Kif5b  (kinesin family member 5B)
Prkar1a  (protein kinase cAMP-dependent type I regulatory subunit alpha)
Prkar2a  (protein kinase cAMP-dependent type II regulatory subunit alpha)
Prkar2b  (protein kinase cAMP-dependent type II regulatory subunit beta)


Additional Information