CHARACTERIZATION AND COMPARISON OF 4 SERINE-RICH AND ARGININE-RICH (SR) PROTEIN-KINASES

Phosphorylated serine-and arginine-rich (SR) proteins are components o f the spliceosomal complex, and have been implicated in the control of alternative splicing. Kinases that regulate the phosphorylation and p ossibly the intranuclear distribution of SR proteins may therefore con tribute to changes in choice of splice site. We have cloned three mous e cDNAs with high sequence identity to the family of LAMMER kinases (i .e. kinases carrying the conserved signature EHLAMMERILG in the cataly tic domain). A comparison of their amino acid sequences revealed two r elated subfamilies with high evolutionary conservation. We have compar ed the expression patterns of these proteins in mouse tissues and tran sformed cell lines with that of a previously cloned family member (mCL K1/STY), and detected various transcripts for each gene. This underlin es previous findings of alternative splicing of mclk1/STY. Our results suggest that the proportions of products for each gene are regulated independently. We further demonstrate that all Variants encode autopho sphorylating proteins that can phosphorylate several biochemically pur ified SR proteins in vitro, leading to hyperphosphorylation of at leas t one SR protein in vivo. The observed tissue distributions and substr ate specificities suggest that these kinases may all be constituents o f a network of regulatory mechanisms that enable SR proteins to contro l RNA splicing.