title: Ras/cAMP-dependent protein kinase (PKA) regulates multiple aspects of cellular events by phosphorylating the Whi3 cell cycle regulator in budding yeast.
abstract: The Start/G1 phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals. In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start. However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown. Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function. Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G1 cyclin mRNA and was required for the promotion of G1/S progression. Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth. Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima City 739-8530, Japan. mmizu49120@hiroshima-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizunuma
authors.forename: Ryohei
authors.initials: R
authors.lastname: Tsubakiyama
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Atsunori
authors.initials: A
authors.lastname: Shitamukai
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Inai
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kume
authors.forename: Dai
authors.initials: D
authors.lastname: Hirata
mesh_terms: D019943:Amino Acid Substitution; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D010766:Phosphorylation / Q000502:physiology; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C440012:Whi3 protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases