title: Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway.
abstract: To cope with life-threatening high osmolarity, yeast activates the high-osmolarity glycerol (HOG) signaling pathway, whose core element is the Hog1 MAP kinase cascade. Activated Hog1 regulates the cell cycle, protein translation, and gene expression. Upstream of the HOG pathway are functionally redundant SLN1 and SHO1 signaling branches. However, neither the osmosensor nor the signal generator of the SHO1 branch has been clearly defined. Here, we show that the mucin-like transmembrane proteins Hkr1 and Msb2 are the potential osmosensors for the SHO1 branch. Hyperactive forms of Hkr1 and Msb2 can activate the HOG pathway only in the presence of Sho1, whereas a hyperactive Sho1 mutant activates the HOG pathway in the absence of both Hkr1 and Msb2, indicating that Hkr1 and Msb2 are the most upstream elements known so far in the SHO1 branch. Hkr1 and Msb2 individually form a complex with Sho1, and, upon high external osmolarity stress, appear to induce Sho1 to generate an intracellular signal. Furthermore, Msb2, but not Hkr1, can also generate an intracellular signal in a Sho1-independent manner.
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Sciences, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tatebayashi
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Yang
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Taichiro
authors.initials: T
authors.lastname: Tomida
authors.forename: Midori
authors.initials: M
authors.lastname: Imai
authors.forename: Haruo
authors.initials: H
authors.lastname: Saito
mesh_terms: D020690:GTPase-Activating Proteins / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009154:Mutation; D009997:Osmotic Pressure; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020690:GTPase-Activating Proteins; C512735:HKR1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C076360:MSB2 protein, S cerevisiae; D008565:Membrane Proteins; C459787:SHO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins