An essential function of a phosphoinositide-specific phospholipase C is relieved by inhibition of a cyclin-dependent protein kinase in the yeast Saccharomyces cerevisiae

• Published in: Genetics (Austin) 1998-01, Vol.148 (1), p.33-47
• Main Authors: Flick, J.S. (Vanderbilt University, Nashville, TN.), Thorner, J
• Format: Article
• Language: English
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Amino Acid Sequence; AMINO ACID SEQUENCES; ANION; ANIONES; ANIONS; ARN MENSAJERO; ARN MESSAGER; Base Sequence; CHEMICAL COMPOSITION; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; Cyclin-Dependent Kinase Inhibitor Proteins; Cyclin-Dependent Kinases - biosynthesis; Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - physiology; Cyclins - metabolism; Deoxyribodipyrimidine Photo-Lyase - genetics; ENZYME INHIBITORS; Enzyme Repression; Enzymes; ENZYMIC ACTIVITY; EPISTASIS; Epistasis, Genetic; ESTERASAS; ESTERASE; ESTERASES; EXPRESION GENICA; EXPRESSION DES GENES; FENOTIPOS; FOSFATOS; FOSFOLIPIDOS; Fungal Proteins - genetics; Fungal Proteins - isolation & purification; Fungal Proteins - metabolism; GENBANK/P38839; GENE; GENE EXPRESSION; Gene Expression Regulation, Fungal; GENE INTERACTION; GENES; Genes, Fungal - genetics; Genes, Fungal - physiology; GENETIC REGULATION; GENETICA; GENETICS; GENETIQUE; INHIBICION; INHIBIDORES DE ENZIMAS; INHIBITEUR D'ENZYME; INHIBITION; INHIBITOR GENES; INTERACCION DE GENES; INTERACTION GENIQUE; MESSENGER RNA; MOLECULAR SEQUENCE DATA; MUTACION; MUTANT; MUTANTES; MUTANTS; MUTATION; NUCLEOTIDE SEQUENCE; PHENOTYPE; PHENOTYPES; PHO81 GENE; PHOSPHATE; PHOSPHATES; Phosphates - metabolism; PHOSPHATIDE; Phosphatidylinositol Diacylglycerol-Lyase; PHOSPHATIDYLINOSITOLS; Phosphoinositide Phospholipase C; PHOSPHOLIPIDS; PROMOTERS; PROTEIN KINASE; PROTEINA QUINASA; PROTEINAS; PROTEINE; PROTEINE KINASE; PROTEINS; Repressor Proteins; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; SECUENCIA NUCLEOTIDICA; Selection, Genetic; Sequence Alignment; Sequence Homology, Amino Acid; SEQUENCE NUCLEOTIDIQUE; SPL1 GENE; SPL2 GENE; Suppression, Genetic; SUPPRESSORS; Temperature; Type C Phospholipases - genetics; Yeast
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/148.1.33

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 plc1delta cell. SPL1 is identical to the PHO81 gene, which encodes an inhibitor of a cyclin (Pho80p)-dependent protein kinase (Pho85p) complex (Cdk). In addition to overproduction of Pho81p, two other conditions that inactivate this Cdk, a cyclin (pho80delta) mutation and growth on low-phosphate medium, also permitted growth of plc1delta cells at the restrictive temperature. Suppression of the temperature sensitivity of plc1delta cells by pho80delta does not depend upon the Pho4p transcriptional regulator, the only known substrate of the Pho80p/Pho85p Cdk. The second suppressor, SPL2, encodes a small (17-kD) protein that bears similarity to the ankyrin repeat regions present in Pho81p and in other known Cdk inhibitors. Both pho81delta and spl2delta show a synthetic phenotype in combination with plc1delta. Unlike single mutants, plc1delta pho81delta and plc1delta spl2delta double mutants were unable to grow on synthetic complete medium, but were able to grow on rich medium.