CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles.

We have isolated and characterised a novel human protein kinase, Cdc2-related kinase with an arginine/serine-rich (RS) domain (CrkRS), that is most closely related to the cyclin-dependent kinase (CDK) family. CrkRS is a 1490 amino acid protein, the largest CDK-related kinase so far isolated. The protein kinase domain of CrkRS is 89% identical to the 46 kDa CHED protein kinase, but outside the kinase domains the two proteins are completely unrelated. CrkRS has extensive proline-rich regions that

match the consensus for SH3 and WW domain binding sites, and an RS domain that is predominantly found in splicing factors. CrkRS is ubiquitously expressed in tissues, and maps to a single genetic locus. There are closely related protein kinases in both the Drosophila and Caenorhabditis elegans genomes. Consistent with the presence of an RS domain, anti-CrkRS antibodies stain nuclei in a speckled pattern, 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 phosphorylate the C-terminal domain of RNA polymerase II in vitro. Thus CrkRS may be a novel, conserved link between the transcription and splicing machinery.[less]