Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ira1 is a negative regulator of Ras proteins in Saccharomyces cerevisiae. Deletion of IRA1 leads to constitutive activation of the Ras/cyclic AMP (cAMP) pathway, which results in several phenotypes including sensitivity to heat-shock (HS) treatment. We have identified eight Schizosaccharomyces pombe cDNAs that, when overexpressed, suppress the HS-sensitive phenotype associated with the deletion of IRA1 in S. cerevisiae. To determine where these cDNAs act, we tested their ability to suppress other mutations that activate the Ras/cAMP pathway in S. cerevisiae. Two of the cDNA clones, pPSI1 and pPSI2, failed to suppress the HS-sensitive phenotype induced by the activating RAS2Val19 mutation. Clone pPSI2 encodes Gap1/Sar1, a Sz. pombe homologue of Ira1, which has been previously identified. Three of the six RAS2Val19 suppressors could suppress the deletion of PDE1 and PDE2, the cAMP phosphodiesterase (Pde)-encoding genes, suggesting that they act downstream from adenylyl cyclase (Cyr). The remaining three clones, pPSI3, pPSI6 and pPSI7, encode proteins that may suppress the HS-sensitive phenotype by reducing Ras and/or Cyr activity. One of these, pPSI3, contains a cDNA that encodes the C-terminal region (aa 166-550) of the Sz. pombe Dbp2 protein, a homologue of the human p68 RNA helicase. We have amplified cDNAs encoding the full-length Sz. pombe Dbp2 protein by the polymerase chain reaction method and have cloned them into a S. cerevisiae expression vector. The ira1- cells harboring these plasmids retained their HS-sensitive phenotype. These results suggest that the truncated Dbp2, but not the full-length protein, is capable of interfering with Ras and/or Cyr activity.
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PMID:Identification and genetic analysis of Schizosaccharomyces pombe cDNAs that suppress deletion of IRA1 in Saccharomyces cerevisiae. 833 53

We previously reported the identification of eight Sz. pombe cDNA clones that are capable of suppressing the heat-shock sensitive phenotype associated with deletion of IRA1 in S. cerevisiae. We report that one of these cDNA clones, pPSI5, encodes a protein, Pde1, that is 24% identical to the S. cerevisiae low-affinity cAMP phosphodiesterase. The pde1/cgs2 gene encoding this protein has been previously identified, and studies have shown that deletion of this gene results in elevated levels of intracellular cAMP and inhibition of meiosis. To demonstrate that Pde1 is a cAMP phosphodiesterase we expressed it in an S. cerevisiae strain which lacks the genomic cAMP phosphodiesterase genes. Extracts from such cells that express the Sz. pombe Pde1 exhibit high levels of cAMP phosphodiesterase activity.
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PMID:The Schizosaccharomyces pombe pde1/cgs2 gene encodes a cyclic AMP phosphodiesterase. 839 46