title: Direct phosphorylation and activation of a Nim1-related kinase Gin4 by Elm1 in budding yeast.
abstract: In budding yeast, Gin4, a Nim1-related kinase, plays an important role in proper organization of the septin ring at the mother-bud neck, a filamentous structure that is critical for diverse cellular processes including mitotic entry and cytokinesis. How Gin4 kinase activity is regulated is not known. Here we showed that a neck-associated Ser/Thr kinase Elm1, which is important for septin assembly, is critical for proper modification of Gin4 and its physiological substrate Shs1. In vitro studies with purified recombinant proteins demonstrated that Elm1 directly phosphorylates and activates Gin4, which in turn phosphorylates Shs1. Consistent with these observations, acute inhibition of Elm1 activity abolished mitotic Gin4 phosphorylation and Gin4-dependent Shs1 modification in vivo. In addition, a gin4 mutant lacking the Elm1-dependent phosphorylation sites exhibited an impaired localization to the bud-neck and, as a result, induced a significant growth defect with an elongated bud morphology. Thus, Elm1 regulates the septin assembly-dependent cellular events by directly phosphorylating and activating the Gin4-dependent pathway(s).
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Krisada
authors.initials: K
authors.lastname: Sakchaisri
authors.forename: Chong J
authors.initials: CJ
authors.lastname: Park
authors.forename: Young H
authors.initials: YH
authors.lastname: Kang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D007313:Insecta; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C411302:ELM1 protein, S cerevisiae; C107283:GIN4 protein, S cerevisiae; C106494:HSL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases