SRPK2 - A DIFFERENTIALLY EXPRESSED SR PROTEIN-SPECIFIC KINASE INVOLVED IN MEDIATING THE INTERACTION AND LOCALIZATION OF PRE-MESSENGER-RNA SPLICING FACTORS IN MAMMALIAN-CELLS

Reversible phosphorylation plays an important role in pre-mRNA splicin g in mammalian cells. Two kinases, SR protein-specific kinase (SRPK1) and Clk/Sty, have been shown to phosphorylate the SR family of splicin g factors. We report here the cloning and characterization of SRPK2, w hich is highly related to SRPK1 in sequence, kinase activity, and subs trate specificity, Random peptide selection for preferred phosphorylat ion sites revealed a stringent preference of SRPK2 for SR dipeptides, and the consensus derived may be used to predict potential phosphoryla tion sites in candidate arginine and serine-rich (RS) domain-containin g proteins. Phosphorylation of an SR protein (ASF/SF2) by either SRPK1 or 2 enhanced its interaction with another RS domain-containing prote in (U1 70K), and overexpression of either kinase induced specific redi stribution of splicing factors in the nucleus. These observations like ly reflect the function of the SRPK family of kinases in spliceosome a ssembly and in mediating the trafficking of splicing factors in mammal ian cells. The biochemical and functional similarities between SRPK1 a nd 2, however, are in contrast to their differences in expression. SRP K1 is highly expressed in pancreas, whereas SRPK2 is highly expressed in brain, although both are coexpressed in other human tissues and in many experimental cell lines. Interestingly, SRPK2 also contains a pro line-rich sequence at its NH2 terminus, and a recent study showed that this NH2-terminal sequence has the capacity to interact with a WW dom ain protein in vitro. Together, our studies suggest that different SRP K family members may be uniquely regulated and targeted, thereby contr ibuting to splicing regulation in different tissues, during developmen t, or in response to signaling.