Protein phosphatase type-1 regulatory subunits Reg1p and Reg2p act as signal transducers in the glucose-induced inactivation of maltose permease in Saccharomyces cerevisiae

The REG1 gene encodes a regulatory subunit of the type-1 protein phosphatas e (PP1) Glc7 in Saccharomyces cerevisiae, which directs the catalytic subun it to substrates involved in glucose repression. Loss of REG1 relieves gluc ose repression of many genes, including the MAL structural genes that encod e the maltose fermentation enzymes. In this report, we explore the role of Reg1p and its homolog Reg2p in glucose-induced inactivation of maltose perm ease. Glucose stimulates the proteolysis of maltose permease and very rapid loss of maltose transport activity - more rapid than can be explained by l oss of the permease protein alone. In a reg1 Delta strain we observe a sign ificantly reduced rate of glucose-induced proteolysis of maltose permease, and the rapid loss of maltose transport activity does not occur. Instead, s urprisingly, the slow rate of proteolysis of maltose permease is accompanie d by an increase in maltose transport activity. Loss of Reg2p modestly redu ces the rates of both glucose-induced proteolysis of maltose permease and i nactivation of maltose transport activity. Overexpression of Reg2p in a I r eg1 Delta 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 gluco se observed in this strain. Thus, protein phosphatase type-1 (Glc7p-Reg1p a nd Glc7p-Reg2p) plays a role in transduction of the glucose signal during g lucose-induced proteolysis of maltose permease, but only Glc7p-Reg1p is inv olved in glucose-induced inactivation of maltose transport activity and glu cose repression of MAL gene expression. Overexpression of REG1 partially re stores proteolysis of maltose permease in a grr1 Delta strain, which lacks glucose signaling, but does not rescue rapid inactivation of maltose transp ort activity or sensitivity to glucose repression. A model for the role of Reg1p and Reg2p in glucose signaling pathways is discussed. We also uncover ed a previously unrecognized G2/M delay in the grr1 Delta but not the reg1 Delta strains, and this delay is suppressed by REG1 overexpression. The G1/ S delay seen in grr1 Delta mutants is slightly suppressed as well, but REG1 overexpression does not suppress other grr1 Delta phenotypes such as insen sitivity to glucose repression.