Download MendeleyInterplay between Srpk and Clk/Sty Kinases in Phosphorylation of the Splicing Factor Asf/Sf2 is Regulated by a Docking Motif in Asf/Sf2
Ngo, J.C., Chakrabarti, S., Ding, J.-H., Velazquez-Dones, A., Nolen, B., Aubol, B.E., Adams, J.A., Fu, X.-D., Ghosh, G.(2005) Mol Cell 20: 77
- PubMed: 16209947
- DOI: https://doi.org/10.1016/j.molcel.2005.08.025
- Primary Citation of Related Structures:
1WBP - PubMed Abstract:
The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the biological regulation of ASF/SF2 is unknown. Here, we report the crystal structure of an active fragment of human SRPK1 bound to a peptide derived from an SR protein. This structure led us to identify a docking motif in ASF/SF2. We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles. We further show that Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the C-terminal part of its RS domain. These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization.
Organizational Affiliation:
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
