AN ESSENTIAL FUNCTION OF A PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C IS RELIEVED BY INHIBITION OF A CYCLIN-DEPENDENT PROTEIN-KINASE IN THE YEAST SACCHAROMYCES-CEREVISIAE

The PLC1 gene product of Saccharomyces cerevisiae is a homolog of the delta isoform of mammalian phosphoinositide-specific phospholipase C ( PI-PLC). We found that two genes (SPL1 and SPL2), when overexpressed, can bypass the temperature-sensitive growth defect of a plc1 Delta cel l. SPL1 is identical to the PH081 gene, which encodes an inhibitor of a cyclin (Pho80p-dependent protein kinase (Pho85p) complex (Cdk). In a ddition to overproduction of Pho81p, two other conditions that inactiv ate this Cdk, a cyclin (pho80 Delta) mutation and growth on low-phosph ate medium, also permitted growth of pho80<Delta cells at the restrict ive temperature. Suppression of tile temperature sensitivity of plc1 D elta cells by pho80 Delta does not depend upon tile Pho4p transcriptio nal regulator the only known substrate of the Pho80p/Pho85p Cdk. The s econd suppressor, SPL2, encodes a small (17-kD) protein that bears sim ilarity to the ankyrin repeat regions present in Pho81p and in other k nown Cdk inhibitors. Both pho81 Delta and spl2 Delta show a synthetic phenotype in combination plc1 Delta. Unlike single mutants, plc1 Delta pho81 Delta and plc1 Delta spl2 Delta double mutants were unable to g row on synthetic complete medium, but were able to grow on rich medium .