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FEMS Yeast Res. 2018 May 1;18(3). doi: 10.1093/femsyr/foy027.

Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.

Author information

1
Department of Chemistry, Tufts University, Medford MA 02155, USA.
2
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge MA 02142, USA.
3
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA.

Abstract

Tyrosine phosphorylation is a key biochemical signal that controls growth and differentiation in multicellular organisms. Saccharomyces cerevisiae and nearly all other unicellular eukaryotes lack intact phosphotyrosine signaling pathways. However, many of these organisms have primitive phosphotyrosine-binding proteins and tyrosine phosphatases, leading to the assumption that the major barrier for emergence of phosphotyrosine signaling was the negative consequences of promiscuous tyrosine kinase activity. In this work, we reveal that the classic oncogene v-Src, which phosphorylates many dozens of proteins in yeast, is toxic because it disrupts a specific spore wall remodeling pathway. Using genetic selections, we find that expression of a specific cyclic peptide, or overexpression of SMK1, a MAP kinase that controls spore wall assembly, both lead to robust growth despite a continuous high level of phosphotyrosine in the yeast proteome. Thus, minimal genetic manipulations allow yeast to tolerate high levels of phosphotyrosine. These results indicate that the introduction of tyrosine kinases within single-celled organisms may not have been a major obstacle to the evolution of phosphotyrosine signaling.

PMID:
29546391
PMCID:
PMC6454501
DOI:
10.1093/femsyr/foy027
[Indexed for MEDLINE]
Free PMC Article

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