title: Glc7-Reg1 phosphatase signals to Yck1,2 casein kinase 1 to regulate transport activity and glucose-induced inactivation of Saccharomyces maltose permease.
abstract: The Saccharomyces casein kinase 1 isoforms encoded by the essential gene pair YCK1 and YCK2 control cell growth and morphogenesis and are linked to the endocytosis of several membrane proteins. Here we define roles for the Yck1,2 kinases in Mal61p maltose permease activation and trafficking, using a yck1delta yck2-2(ts) (yck(ts)) strain with conditional Yck activity. Moreover, we provide evidence that Glc7-Reg1 phosphatase acts as an upstream activator of Yck1,2 kinases in a novel signaling pathway that modulates kinase activity in response to carbon source availability. The yck(ts) strain exhibits significantly reduced maltose transport activity despite apparently normal levels and cell surface localization of maltose permease protein. Glucose-induced internalization and rapid loss of maltose transport activity of Mal61/HAp-GFP are not observed in the yck(ts) strain and maltose permease proteolysis is blocked. We show that a reg1delta mutant exhibits a phenotype remarkably similar to that conferred by yck(ts). The reg1delta phenotype is not enhanced in the yck(ts) reg1delta double mutant and is suppressed by increased Yck1,2p dosage. Further, although Yck2p localization and abundance do not change in the reg1delta mutant, Yck1,2 kinase activity, as assayed by glucose-induced HXT1 expression and Mth1 repressor stability, is substantially reduced in the reg1delta strain.
authors.affiliation: Biology Department, Queens College and the Graduate School of CUNY, Flushing, New York 11367, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gadura
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Robinson
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Michels
mesh_terms: D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D047389:Casein Kinase I / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D004794:Enzyme Repression / Q000235:genetics; D004843:Epistasis, Genetic; D005947:Glucose / Q000737:chemistry / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009154:Mutation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics; D012440:Saccharomyces / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: C084434:DOA4 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D009004:Monosaccharide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D002244:Carbon; C021534:maltose permease; D047389:Casein Kinase I; C479664:YCK1 protein, S cerevisiae; C479666:YCK2 protein, S cerevisiae; C092048:GLC7 protein, S cerevisiae; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D005947:Glucose