Amino acid transport through the Saccharomyces cerevisiae Gap1 permease is controlled by the Ras/cAMP pathway

The general amino acid permease (Gap1p) of Saccharomyces cerevisiae is a broad range, low affinity permease that imports amino acids in cells growing on poor nitrogen sources. This permease also signals the presence of amino acids through the fermentable growth medium pathway allowing the cell to respond to new sources of nitrogen in the surrounding medium. Yeast with an activated Ras2/cAMP pathway show many phenotypes indicative of altered nitrogen uptake and metabolism; sensitivity to nitrogen starvation, low amino acid pools. We have shown that Gap1p activity is lowered in cells with an activated RAS2(val19) allele or elevated cAMP levels whereas cells with inactive ras2 allele lose ammonia repression of Gap1p-mediated transport. This regulation is through a post-transcriptional mechanism; transcription of GAP1 is not affected by cAMP level. A mechanism by which the Ras2/cAMP/PKA pathway controls the ubiquitin-dependent degradation of Gap1p is most consistent with the data.