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A more recent version of this article appeared on February 1, 2006
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Submitted on October 18, 2005
Accepted on November 21, 2005
Departments of *Cellular and Molecular Medicine, Pharmacology, and Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0651
Monitoring Editor: Joseph Gall
Reversible phosphorylation of the SR family of splicing factors plays an important pre-mRNA prcessing in the nucleus. Interestingly, the SRPK family of kinases specific for SR proteins is localized in the cytoplasm, which is critical for nuclear import of SR proteins in a phosphorylated dependent manner. Here, we report molecular dissection of the mechanism involved in partitioning SRPKs in the cytoplasm. Common among all SRPKs, the bipartite kinase catalytic core is separated by a unique spacer sequence. The spacers in mammalian SRPK1 and SRPK2 share little sequence homology, but function interchangeably in restricting the kinases in the cytoplasm. Removal of the spacer in SRPK1 had little effect on the kinase activity, but caused a quantitative translocation of the kinase to the nucleus, and consequently, induced aggregation of splicing factors in the nucleus. Rather than carrying an NES as previously suggested, we found multiple redundant signals in the spacer that act together to anchor the kinase in the cytoplasm. Interestingly, a cell cycle signal induced nuclear translocation of the kianse by at the G2/M boundary. These findings suggest that SRPKs may play an important role in linking signaling to RNA metabolism in higher eukaryotic cells.
These authors contributed equally to this work.
Address correspondence to:
Xiang-Dong Fu (xdfu{at}ucsd.edu)
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