Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras

Nature. 1992 Dec;360(6406):762-5. doi: 10.1038/360762a0.

Abstract

In the yeast Sacchromyces cerevisiae, addition of glucose to starved cells triggers a transient rise in the intracellular level of cyclic AMP that induces a protein phosphorylation cascade. The glucose signal is processed by the Cdc25/Ras/adenylyl cyclase pathway, where the role of Cdc25 is to catalyse the GDP-GTP exchange on Ras. The molecular mechanisms involved in the regulation of the activity of Cdc25 are unknown. We report here the use of highly selective anti-Cdc25 antibodies to demonstrate that Cdc25 is a phospho protein and that in response to glucose it is hyperphosphorylated, within seconds, by the cyclic AMP-dependent protein kinase. It is also demonstrated that, concomitantly with hyperphosphorylation, Cdc25 partially relocalizes to the cytoplasm, reducing its accessibility to membrane-bound Ras. These results are of general significance because of the highly conserved sequence of Ras-guanyl nucleotide exchange factors from yeasts to mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Cell Cycle Proteins*
  • Cell Membrane / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cytoplasm / metabolism
  • Fungal Proteins / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Glucose / pharmacology*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Immunosorbent Techniques
  • Phosphorylation
  • Protein Kinases / metabolism
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae Proteins
  • ras Proteins*
  • ras-GRF1*

Substances

  • CDC25 protein, S cerevisiae
  • Cell Cycle Proteins
  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins
  • ras-GRF1
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Cyclic AMP
  • Protein Kinases
  • GTP-Binding Proteins
  • ras Proteins
  • Adenylyl Cyclases
  • Glucose