The PITSLRE protein kinases, hereafter referred to as cyclin-dependent kinase 11 (CDK11) due to their association with cyclin L, are part of large molecular weight protein complexes that contain RNA polymerase II (RNAP II) as well as numerous transcription and RNA processing factors. Data presented here demonstrate that the influence of CDK11p110 on transcription and splicing does not involve phosphorylation of the RNAP II carboxyl-terminal domain by CDK11p110. We have isolated a DRB- and heparin-sensitive protein kinase activity that co-purifies with CDK11p110 after ion exchange and affinity purification chromatography. This protein kinase was identified as casein kinase 2 (CK2) by immunoblot and mass spectrometry analyses. In addition to the RNAP II carboxyl-terminal domain, CK2 phosphorylates the CDK11p110 amino-terminal domain. These data suggest that CDK11p110 isoforms participate in signaling pathways that include CK2 and that its function may help to coordinate the regulation of RNA transcription and processing events. Future experiments will determine how phosphorylation of CDK11p110 by CK2 specifically affects RNA transcription and/or processing events.