Homologous activators of ras in fission and budding yeast

THE ras proto-oncogene products are plasma membrane-bound, guanine nucleotide-binding proteins implicated in signal transduction across the plasma membrane1. But the signal(s) that activates the ras pathway(s) is not known. In the budding yeast Saccharomyces cerevisiae, the CDC25 gene product acts upstream of Ras proteins2,3, but it has not been clear whether CDC25 function is unique to the S. cerevisiae ras pathway. Here we report that the ste6 gene of fission yeast Schizosaccharomyces pombe is a homologue of CDC25: the ste6 gene product and the CDC25 gene product have significant amino-acid similarity in their C-terminal regions. Like the S. pombe ras1gene4,5, ste6 is essential for mating6. Epistatic interactions indicate that the ste6 gene functions upstream of ras1. We propose that ste6 and CDC25 activate Ras protein through a common mechanism, perhaps by promoting GDP-GTP exchange, even though it seems that the function of Ras protein in budding yeast differs from that in fission yeast. Homologues of ste6 and CDC25 could regulate ras activity in other eukaryotic cells.

[1]  S. Henikoff.  Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. , 1984, Gene.

[2]  Y. Kaziro,et al.  Mating pheromone‐like diffusible factor released by Schizosaccharomyces pombe , 1986, The EMBO journal.

[3]  C. Richardson,et al.  DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Jacquet,et al.  A new RAS mutation that suppresses the CDC25 gene requirement for growth of Saccharomyces cerevisiae , 1988, Molecular and cellular biology.

[5]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Robert C. King,et al.  Handbook of Genetics , 1976, Springer US.

[7]  K. Murata,et al.  Transformation of intact yeast cells treated with alkali cations , 1983 .

[8]  D. Beach,et al.  Involvement of ras in sexual differentiation but not in growth control in fission yeast , 1986, The EMBO journal.

[9]  A. Pingoud,et al.  The guanine‐nucleotide binding proteins EMBO‐NATO‐CEC advanced research workshop organized by L. Bosch, B. Kraal and A. Parmeggiani in Renesse, The Netherlands, August 6–11, 1988 , 1988, FEBS letters.

[10]  H. Michael,et al.  Sterility (ste) genes of Schizosaccharomyces pombe , 1987 .

[11]  P. Thuriaux,et al.  Genetical analysis of a sterile mutant by protoplast fusion in the fission yeast Schizosaccharomyces pombe. , 1980, Journal of general microbiology.

[12]  M. Jacquet,et al.  Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. , 1986, The EMBO journal.

[13]  M. Yamamoto,et al.  Characterization of the Schizosaccharomyces pombe ral2 gene implicated in activation of the ras1 gene product , 1989, Molecular and cellular biology.

[14]  M. Yamamoto,et al.  Role of a ras homolog in the life cycle of schizosaccharomyces pombe , 1986, Cell.

[15]  M. Jacquet,et al.  The Cyclic Amp Producing Pathway in Saccharomyces Cerevisiae Involves CDC25 and ras Genes Products , 1989 .

[16]  M. Jacquet,et al.  The C-terminal part of a gene partially homologous to CDC 25 gene suppresses the cdc25-5 mutation in Saccharomyces cerevisiae. , 1989, Gene.

[17]  M. Wigler,et al.  Dominant yeast and mammalian RAS mutants that interfere with the CDC25-dependent activation of wild-type RAS in Saccharomyces cerevisiae , 1989, Molecular and cellular biology.

[18]  R. Rothstein.  One-step gene disruption in yeast. , 1983, Methods in enzymology.

[19]  J. Vieira,et al.  Production of single-stranded plasmid DNA. , 1987, Methods in enzymology.

[20]  M. Wigler,et al.  The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway , 1987, Cell.

[21]  L. C. Robinson,et al.  CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. , 1987, Science.

[22]  D. Lipman,et al.  Rapid and sensitive protein similarity searches. , 1985, Science.