The Saccharomyces SHP1 Gene, Which Encodes a Regulator of Phosphoprotein Phosphatase 1 with Differential Effects on Glycogen Metabolism, Meiotic Differentiation, and Mitotic Cell Cycle Progression

Abstract

The phosphoprotein phosphatase 1 (PP1) catalytic subunit encoded by the Saccharomyces GLC7 gene is involved in control of glycogen metabolism, meiosis, translation, chromosome segregation, cell polarity, and G₂/M cell cycle progression. It is also lethal when overproduced. We have isolated strains which are resistant to Glc7p overproduction lethality as a result of mutations in the SHP1 (suppressor of high-copy PP1) gene, which was previously encountered in a genomic sequencing project as an open reading frame whose interruption totally blocked sporulation and slightly slowed cell proliferation. These phenotypes also characterized our shp1 mutations, as did deficient glycogen accumulation. Lysates from the shp1 mutants were deficient in PP1 catalytic activity but exhibited no obvious abnormalities in the steady-state level or subcellular localization pattern of a catalytically active Glc7p-hemagglutinin fusion polypeptide. The lower level of PP1 activity in shp1 cells permitted substitution of a galactose-induced GAL10-GLC7 fusion for GLC7; depletion of Glc7p from these cells by growth in glucose medium resulted in G₂/M arrest as previously observed for a glc7^cs allele but with depletion arrest occurring most frequently at a later stage of mitosis. The higher requirement of glycogen accumulation and sporulation for PP1 activity would permit their regulation via Glc7p activity, independent of its requirement for mitosis.