The Yeast LATS/Ndr Kinase Cbk1 Regulates Growth via Golgi-dependent Glycosylation and Secretion
| Autor: | Kevan M. Shokat, Nattha Wannissorn, Venkata K. Kuravi, Michelle Husain, J. Michael McCaffery, Chao Zhang, Pavel A. Nazarov, Cornelia Kurischko, Francis C. Luca |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Glycosylation
Saccharomyces cerevisiae Proteins Recombinant Fusion Proteins Golgi Apparatus Cell Cycle Proteins Pyridinium Compounds Saccharomyces cerevisiae Biology Protein Serine-Threonine Kinases Mannosyltransferases Exocytosis Fungal Proteins symbols.namesake chemistry.chemical_compound GTP-binding protein regulators GTP-Binding Proteins Cell polarity Guanine Nucleotide Exchange Factors Secretion Protein kinase A Molecular Biology Cytoskeleton Fluorescent Dyes Anthelmintics NDR kinase Membrane Glycoproteins Glucan Endo-1 3-beta-D-Glucosidase Cell Cycle Intracellular Signaling Peptides and Proteins Cell Polarity Cell Biology Articles Golgi apparatus Protein-Tyrosine Kinases Cell biology Quaternary Ammonium Compounds Phenotype chemistry rab GTP-Binding Proteins Vacuoles symbols Hygromycin B |
| Popis: | Saccharomyces cerevisiae Cbk1 is a LATS/Ndr protein kinase and a downstream component of the regulation of Ace2 and morphogenesis (RAM) signaling network. Cbk1 and the RAM network are required for cellular morphogenesis, cell separation, and maintenance of cell integrity. Here, we examine the phenotypes of conditional cbk1 mutants to determine the essential function of Cbk1. Cbk1 inhibition severely disrupts growth and protein secretion, and triggers the Swe1-dependent morphogenesis checkpoint. Cbk1 inhibition also delays the polarity establishment of the exocytosis regulators Rab-GTPase Sec4 and its exchange factor Sec2, but it does not interfere with actin polarity establishment. Cbk1 binds to and phosphorylates Sec2, suggesting that it regulates Sec4-dependent exocytosis. Intriguingly, Cbk1 inhibition causes a >30% decrease in post-Golgi vesicle accumulation in late secretion mutants, indicating that Cbk1 also functions upstream of Sec2-Sec4, perhaps at the level of the Golgi. In agreement, conditional cbk1 mutants mislocalize the cis-Golgi mannosyltransferase Och1, are hypersensitive to the aminoglycoside hygromycin B, and exhibit diminished invertase and Sim1 glycosylation. Significantly, the conditional lethality and hygromycin B sensitivity of cbk1 mutants are suppressed by moderate overexpression of several Golgi mannosyltransferases. These data suggest that an important function for Cbk1 and the RAM signaling network is to regulate growth and secretion via Golgi and Sec2/Sec4-dependent processes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|