CrkRS: a novel conserved Cdc2-related protein kinase that colocalises withSC35 speckles

We have isolated and characterised a novel human protein kinase, Cdc2-relat ed kinase with an arginine/serine-rich (RS) domain (CrkRS), that is most cl osely related to the cyclin-dependent kinase (CDK) family. CrkRS is a 1490 amino acid protein, the largest CDK-related kinase so far isolated. The pro tein kinase domain of CrkRS is 89% identical to the 46 kDa CHED protein kin ase, but outside the kinase domains the two proteins are completely unrelat ed. CrkRS has extensive proline-rich regions that match the consensus for S H3 and WW domain binding sites, and an RS domain that is predominantly foun d in splicing factors. CrkRS is ubiquitously expressed in tissues,,and maps to a single genetic locus. There are closely related protein kinases in bo th the Drosophila and Caenorhabditis elegans genomes. Consistent with the p resence of an RS domain, anti-CrkRS antibodies stain nuclei in a speckled p attern, overlapping with spliceosome components and the hyperphosphorylated form of RNA polymerase II. Like RNA polymerase II, CrkRS is a constitutive MPM-2 antigen throughout the cell cycle. Anti-CrkRS immunoprecipitates pho sphorylate the C-terminal domain of RNA polymerase II in vitro. Thus CrkRS may be a novel, conserved link between the transcription and splicing machi nery.