RPK1, AN ESSENTIAL YEAST PROTEIN-KINASE INVOLVED IN THE REGULATION OFTHE ONSET OF MITOSIS, SHOWS HOMOLOGY TO MAMMALIAN DUAL-SPECIFICITY KINASES

We report here the sequence of RPK1 (for Regulatory cell Proliferation Kinase), a new Saccharomyces cerevisiae gene coding for a protein wit h sequence similarities to serine/threonine protein kinases. The prote in sequence of 764 amino acids includes an amino-terminal domain (resi dues 1-410), which may be involved in regulation of the kinase domain (residues 411-764). The catalytic domain of Rpk1 is not closely relate d to other known yeast protein kinases but exhibits strong homology to a newly discovered group of mammalian kinases (PYT, TTK, esk) with se rine/ threonine/tyrosine kinase activity. Null alleles of RPK1 are let hal and thus this gene belongs to the small group of yeast protein kin ase genes that are essential for cell growth. In addition, eliminating the expression of RPK1 gives rise to the accumulation of non-viable c ells with less than a 1 N DNA content suggesting that cells proceed in to mitosis without completion of DNA synthesis. Therefore, the Rpk1 ki nase may function in a checkpoint control which couples DNA replicatio n to mitosis. The level of the RPK1 transcript is extremely low and co nstant throughout the mitotic cycle. However it is regulated during ce llular differentiation, being decreased in alpha-factor-treated a cell s and increased late in meiosis in a/alpha diploids. Taken together, o ur results suggest that Rpk1 is involved in a pathway that coordinates cell proliferation and differentiation.