14-3-3 Proteins: Potential Roles in Vesicular Transport and Ras Signaling in Saccharomyces cerevisiae

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-12, Vol.92 (25), p.11539-11543
• Main Authors: Gelperin, Daniel, Weigle, Jeffrey, Nelson, Karen, Roseboom, Patrick, Irie, Kenji, Matsumoto, Kunihiro, Lemmon, Sandra
• Format: Article
• Language: English
• Subjects: 14-3-3 Proteins; Amino Acid Sequence; Biological Transport - genetics; Cell growth; Cellular biology; Clathrin - deficiency; Clathrin - genetics; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Dosage; Gene Expression Regulation, Fungal; Genetic mutation; Intracellular Membranes - metabolism; Molecular Sequence Data; Mutagenesis; Phenotypes; Plasmids; Protein isoforms; Proteins; Proteins - genetics; ras Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - radiation effects; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Signal Transduction; Suppression, Genetic; Tyrosine 3-Monooxygenase; Ultraviolet Rays; Viability; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.25.11539

Deletion of the clathrin heavy-chain gene, CHC1, in the budding yeast Saccharomyces cerevisiae results in growth, morphological, and membrane trafficking defects, and in some strains chc1-Δ is lethal. A previous study identified five genes which, in multicopy, rescue inviable strains of Chc-yeast. Now we report that one of the suppressor loci, BMH2/SCD3, encodes a protein of the 14-3-3 family. The 14-3-3 proteins are abundant acidic proteins of ≈30 kDa with numerous isoforms and a diverse array of reported functions. The Bmh2 protein is >70% identical to the mammalian ε-isoform and >90% identical to a previously reported yeast 14-3-3 protein encoded by BMH1. Single deletions of BMH1 or BMH2 have no discernible phenotypes, but deletion of both BMH1 and BMH2 is lethal. High-copy BMH1 also rescues inviable strains of Chc-yeast, although not as well as BMH2. In addition, the slow growth of viable strains of Chc-yeast is further impaired when combined with single bmh mutations, often resulting in lethality. Overexpression of BMH genes also partially suppresses the temperature sensitivity of the cdc25-1 mutant, and high-copy TPK1, encoding a cAMP-dependent protein kinase, restores Bmh-yeast to viability. High-copy TPK1 did not rescue Chc-yeast. These genetic interactions suggest that budding-yeast 14-3-3 proteins are multifunctional and may play a role in both vesicular transport and Ras signaling pathways.