| First Author | Day ME | Year | 2011 |
| Journal | J Cell Biol | Volume | 193 |
| Issue | 2 | Pages | 347-63 |
| PubMed ID | 21502359 | Mgi Jnum | J:177007 |
| Mgi Id | MGI:5293291 | Doi | 10.1083/jcb.201010034 |
| Citation | Day ME, et al. (2011) Isoform-specific targeting of PKA to multivesicular bodies. J Cell Biol 193(2):347-63 |
| abstractText | Although RII protein kinase A (PKA) regulatory subunits are constitutively localized to discrete cellular compartments through binding to A-kinase-anchoring proteins (AKAPs), RI subunits are primarily diffuse in the cytoplasm. In this paper, we report a novel AKAP-dependent localization of RIalpha to distinct organelles, specifically, multivesicular bodies (MVBs). This localization depends on binding to AKAP11, which binds tightly to free RIalpha or RIalpha in complex with catalytic subunit (holoenzyme). However, recruitment to MVBs occurs only with the release of PKA catalytic subunit (PKAc). This recruitment is reversed by reassociation with PKAc, and it is disrupted by the presence of AKAP peptides, mutations in the RIalpha AKAP-binding site, or knockdown of AKAP11. Cyclic adenosine monophosphate binding not only unleashes active PKAc but also leads to the targeting of AKAP11:RIalpha to MVBs. Therefore, we show that the RIalpha holoenzyme is part of a signaling complex with AKAP11, in which AKAP11 may direct RIalpha functionality after disassociation from PKAc. This model defines a new paradigm for PKA signaling. |
