PITALRE, A NUCLEAR CDC2-RELATED PROTEIN-KINASE THAT PHOSPHORYLATES THE RETINOBLASTOMA PROTEIN IN-VITRO

Members of the cell division cycle 2 (CDC2) family of kinases play a p ivotal role in the regulation of the eukaryotic cell cycle. In this co mmunication, we report the isolation of a cDNA that encodes a CDC2-rel ated human protein kinase temporarily designated PITALRE for the chara cteristic Pro-Ile-Thr-Ala-Leu-Arg-Glu moth. Its deduced amino acid seq uence is 47% identical to that of the human cholinesterase related cel l division controller (CHED) kinase, which is required during hematopo iesis, and 42% identical to the Saccharomyces cerevisiae SGV1 gene pro duct, a putative kinase involved in the response to pheromone via its guanine nucleotide-binding protein alpha subunit. PITALRE expression i s ubiquitous, but its expression levels are different in various human tissues. PITALRE is an approximate to 43-kDa protein that associates with three cellular polypeptides of 80, 95, and 155 kDa. PITALRE is lo calized primarily to the nucleus. In addition, we have identified a re tinoblastoma protein kinase activity associated with PITALRE immunocom plexes that cannot phosphorylate histone H1, suggesting that the targe t phosphorylation site of PITALRE differs from that of CDC2 kinase. In terestingly, the retinoblastoma kinase activity associated with PITALR E does not oscillate during the cell cycle.