Isoform-specific targeting of PKA to multivesicular bodies
| Autor: | Mark H. Ellisman, Mira Sastri, John D. Scott, Susan S. Taylor, Mason R. Mackey, Michele E. Day, Guido M. Gaietta, Antonius Koller, Guy Perkins |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
endocrine system
Protein subunit Molecular Sequence Data A Kinase Anchor Proteins Plasma protein binding Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Catalytic Domain Humans Cyclic adenosine monophosphate Amino Acid Sequence Binding site Protein kinase A Research Articles 030304 developmental biology 0303 health sciences Binding Sites Multivesicular Bodies Cell Biology Cyclic AMP-Dependent Protein Kinases Transport protein Cell biology Isoenzymes Protein Transport HEK293 Cells chemistry Cytoplasm 030220 oncology & carcinogenesis Gene Knockdown Techniques Mutation HeLa Cells Protein Binding Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | PKA RIα subunit is localized to MVBs by the A-kinase–anchoring protein AKAP11 when disassociated from the PKA catalytic subunit. 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 RIα to distinct organelles, specifically, multivesicular bodies (MVBs). This localization depends on binding to AKAP11, which binds tightly to free RIα or RIα 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 RIα AKAP-binding site, or knockdown of AKAP11. Cyclic adenosine monophosphate binding not only unleashes active PKAc but also leads to the targeting of AKAP11:RIα to MVBs. Therefore, we show that the RIα holoenzyme is part of a signaling complex with AKAP11, in which AKAP11 may direct RIα functionality after disassociation from PKAc. This model defines a new paradigm for PKA signaling. |
| Databáze: | OpenAIRE |
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