RGD Reference Report - The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain. - Rat Genome Database

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The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain.

Authors: Piggott, LA  Bauman, AL  Scott, JD  Dessauer, CW 
Citation: Piggott LA, etal., Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13835-40. Epub 2008 Sep 4.
RGD ID: 2313147
Pubmed: PMID:18772391   (View Abstract at PubMed)
PMCID: PMC2544540   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0712100105   (Journal Full-text)

A-kinase anchoring proteins (AKAPs) influence the spatial and temporal regulation of cAMP signaling events. Anchoring of PKA in proximity to certain adenylyl cyclase (AC) isoforms is thought to enhance the phosphorylation dependent termination of cAMP synthesis. Using a combination of immunoprecipitation and enzymological approaches, we show that the plasma membrane targeted anchoring protein AKAP9/Yotiao displays unique specificity for interaction and the regulation of a variety of AC isoforms. Yotiao inhibits AC 2 and 3, but has no effect on AC 1 or 9, serving purely as a scaffold for these latter isoforms. Thus, Yotiao represents an inhibitor of AC2. The N terminus of AC2 (AC2-NT), which binds directly to amino acids 808-957 of Yotiao, mediates this interaction. Additionally, AC2-NT and Yotiao (808-957) are able to effectively inhibit the association of AC2 with Yotiao and, thus, reverse the inhibition of AC2 by Yotiao in membranes. Finally, disruption of Yotiao-AC interactions gives rise to a 40% increase in brain AC activity, indicating that this anchoring protein functions to directly regulate cAMP production in the brain.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of adenylate cyclase activity  IMP 2313147 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q99996-42313147PMID:18772391IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Adcy2  (adenylate cyclase 2)
Akap9  (A-kinase anchoring protein 9)

Additional Information