Splicing Factor Arginine/Serine-rich 17A (SFRS17A) Is an A-kinase Anchoring Protein That Targets Protein Kinase A to Splicing Factor Compartments*
- Elisabeth Jarnæss‡§,1,
- Anne Jorunn Stokka‡§,
- Anne-Katrine Kvissel¶‖,
- Bjørn S. Skålhegg¶‖,
- Knut Martin Torgersen‡§,
- John D. Scott**,
- Cathrine R. Carlson‡,2 and
- Kjetil Taskén‡§,3
- From the ‡Biotechnology Centre of Oslo,
- the §Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership,
- the ¶Department of Nutrition, and
- the ‖Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, PB 1125 Blindern, N-0317 Oslo, Norway and
- the **Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195
- ↵3 To whom correspondence should be addressed: The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125, Blindern, N-0317 Oslo, Norway. Tel.: 47-22840505; Fax: 47-22840506; E-mail: kjetil.tasken{at}biotek.uio.no.
Abstract
Protein kinase A (PKA) is targeted to distinct subcellular localizations by specific protein kinase A anchoring proteins (AKAPs). AKAPs are divided into subclasses based on their ability to bind type I or type II PKA or both. Dual-specificity AKAPs were recently reported to have an additional PKA binding determinant called the RI specifier region. A bioinformatic search with the consensus RI specifier region identified a novel AKAP, the splicing factor arginine/serine-rich 17A (SFRS17A). Here, we show by a variety of protein interaction assays that SFRS17A binds both type I and type II PKA in vitro and inside cells, demonstrating that SFRS17A is a dual-specific AKAP. Moreover, immunofluorescence experiments show that SFRS17A colocalizes with the catalytic subunit of PKA as well as the splicing factor SC35 in splicing factor compartments. Using the E1A minigene splicing assay, we found that expression of wild type SFRS17A conferred regulation of E1A alternative splicing, whereas the mutant SFRS17A, which is unable to bind PKA, did not. Our data suggest that SFRS17A is an AKAP involved in regulation of pre-mRNA splicing possibly by docking a pool of PKA in splicing factor compartments.
Footnotes
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↵1 A fellow of The University of Oslo.
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↵* This work was supported by grants from the Norwegian Functional Genomics Program, the Research Council of Norway, the Norwegian Cancer Society, Novo Nordic Foundation, and European Union Grant 037189 (thera-cAMP). This work was also supported, in part by National Institutes of Health Grant DK54441 (to J. D. S.).
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The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1 and Figs. S1 and S2.
- Received August 16, 2009.
- Revision received October 19, 2009.
- © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
