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Vol. 17, Issue 2, 876-885, February 2006

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Regulated Cellular Partitioning of SR Protein-specific Kinases in Mammalian Cells

Jian-Hua Ding ^* , Xiang-Yang Zhong ^* , Jonathan C. Hagopian , Marissa M. Cruz ^*, Gourisankar Ghosh , James Feramisco ^* , Joseph A. Adams , and Xiang-Dong Fu ^*

^* Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0651; and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0651

Submitted October 18, 2005; Accepted November 21, 2005
Monitoring Editor: Joseph Gall

Reversible phosphorylation of the SR family of splicing factors plays an important role in pre-mRNA processing 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 phosphorylation-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 they function interchangeably in restricting the kinases in the cytoplasm. Removal of the spacer in SRPK1 had little effect on the kinase activity, but it caused a quantitative translocation of the kinase to the nucleus and consequently induced aggregation of splicing factors in the nucleus. Rather than carrying a nuclear export signal as suggested previously, 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 kinase 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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