The KH-Tudor domain of a-kinase anchoring protein 149 mediates RNA-dependent self-association.
A-Kinase anchoring proteins (AKAPs) control the subcellular localization and temporal specificity of protein phosphorylation mediated by cAMP-dependent protein kinase. AKAP149 (AKAP1) is found in mitochondria and in the endoplasmic reticulum-nuclear envelope network where it anchors protein kinases, phosphatases, and a phosphodiesterase. AKAP149 harbors in its COOH-terminal part one KH and one Tudor domain, both known to be involved in RNA binding. We investigated the properties of the COOH-terminal domain of AKAP149. We show here that AKAP149 is a self-associating protein with RNA binding features. The KH domain of AKAP149 is sufficient for self-association in a RNA-dependent manner. The Tudor domain is not necessary for self-association, but it is required together with the KH domain for targeting to well-defined nuclear foci. These foci are spatially closely related to nucleolar subcompartments. We also show that the KH-Tudor-containing domain of AKAP149 binds RNA in vitro and in RNA coprecipitation experiments. AKAP149 emerges as a scaffolding protein involved in the integration of intracellular signals and possibly in RNA metabolism.
Rogne
Marie
M
Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway.
Landsverk
Helga B
HB
Van Eynde
Aleyde
A
Beullens
Monique
M
Bollen
Mathieu
M
Collas
Philippe
P
Küntziger
Thomas
T
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017510:Protein Folding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C486333:Akap1 protein, mouse; D016601:RNA-Binding Proteins; D012313:RNA; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases