PKA-dependent binding of mRNA to the mitochondrial AKAP121 protein.
Protein kinase A (PKA) anchoring proteins (AKAPs) tether PKA to various subcellular locations. AKAP121, which tethers PKAII to the outer mitochondrial membrane, includes a K homology (KH) RNA-binding motif. Purified AKAP121 KH domain binds the 3' untranslated regions (3'UTRs) of transcripts encoding the Fo-f subunit of mitochondrial ATP synthase and manganese superoxide dismutase (MnSOD). Binding requires a structural motif in the 3'UTR and is stimulated by PKA phosphorylation of the domain or a mutation that mimics this phosphorylation. AKAP121 expressed in HeLa cells promotes the translocation of MnSOD mRNA from cytosol to mitochondria and an increase in mitochondrial MnSOD. Both reactions are stimulated by cAMP. Thus, by focusing translation at the mitochondrial membrane, AKAP121 may facilitate import of mitochondrial proteins in response to cAMP stimulation.
Ginsberg
Michael D
MD
Institute of Cancer Research, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, NY 10032, USA.
Feliciello
Antonio
A
Jones
Jeffrey K
JK
Avvedimento
Enrico V
EV
Gottesman
Max E
ME
D020413:3' Untranslated Regions / Q000737:chemistry / Q000378:metabolism; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D009842:Oligopeptides / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D020413:3' Untranslated Regions; D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008024:Ligands; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D021122:Protein Subunits; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C037642:kemptide; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D017868:Cyclic AMP-Dependent Protein Kinases; D025261:Mitochondrial Proton-Translocating ATPases