title: Protein phosphatase type-1 regulatory subunits Reg1p and Reg2p act as signal transducers in the glucose-induced inactivation of maltose permease in Saccharomyces cerevisiae.
abstract: The REG1 gene encodes a regulatory subunit of the type-1 protein phosphatase (PP1) G1c7 in Saccharomyces cerevisiae, which directs the catalytic subunit to substrates involved in glucose repression. Loss of REG1 relieves glucose repression of many genes, including the MAL structural genes that encode the maltose fermentation enzymes. In this report, we explore the role of Reglp and its homolog Reg2p in glucose-induced inactivation of maltose permease. Glucose stimulates the proteolysis of maltose permease and very rapid loss of maltose transport activity - more rapid than can be explained by loss of the permease protein alone. In a reg1delta strain we observe a significantly reduced rate of glucose-induced proteolysis of maltose permease, and the rapid loss of maltose transport activity does not occur. Instead, surprisingly, the slow rate of proteolysis of maltose permease is accompanied by an increase in maltose transport activity. Loss of Reg2p modestly reduces the rates of both glucose-induced proteolysis of maltose permease and inactivation of maltose transport activity. Overexpression of Reg2p in a reg1delta strain suppresses the effect on maltose permease proteolysis and partially restores the inactivation of maltose transport activity, but does not affect the insensitivity of MAL gene expression to repression by glucose observed in this strain. Thus, protein phosphatase type-1 (Glc7p-Reglp and Glc7p-Reg2p) plays a role in transduction of the glucose signal during glucose-induced proteolysis of maltose permease, but only Glc7p-Reglp is involved in glucose-induced inactivation of maltose transport activity and glucose repression of MAL gene expression. Overexpression of REG1 partially restores proteolysis of maltose permease in a grr1delta strain, which lacks glucose signaling, but does not rescue rapid inactivation of maltose transport activity or sensitivity to glucose repression. A model for the role of Reglp and Reg2p in glucose signaling pathways is discussed. We also uncovered a previously unrecognized G2/M delay in the grr1delta but not the reg1delta strains, and this delay is suppressed by REG1 overexpression. The G1/S delay seen in grr1delta mutants is slightly suppressed as well, but REG1 overexpression does not suppress other grr1delta phenotypes such as insensitivity to glucose repression.
authors.affiliation: Biology Department, Queens College and Graduate School of CUNY, Flushing, NY 11367, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Tatchell
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: C A
authors.initials: CA
authors.lastname: Michels
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins; D002453:Cell Cycle; D004789:Enzyme Activation; D044783:F-Box Proteins; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000502:physiology; D005838:Genotype; D005947:Glucose / Q000494:pharmacology*; D007700:Kinetics; D008320:Maltose / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D044783:F-Box Proteins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C071032:GRR1 protein, S cerevisiae; D008320:Maltose; C021534:maltose permease; D044767:Ubiquitin-Protein Ligases; D010749:Phosphoprotein Phosphatases; D000520:alpha-Glucosidases; D005947:Glucose