SUMMARY PARAGRAPH for CYR1
In S. cerevisiae, growth and metabolism in response to nutrients, particularly glucose, is regulated to a large degree by the Ras/cyclic AMP (cAMP) pathway (reviewed in 6). CYR1 encodes adenylate cyclase, the enzyme that synthesizes cAMP from ATP (2). Through its role in increasing cAMP levels to activate cAMP-dependent protein kinase, Cyr1p is involved in nutrient signaling, cell cycle progression, sporulation, cell growth, stress response, and longevity (3 and reviewed in 7 and 8). In response to nutrients, Cyr1p is activated through the concerted actions of the cyclase associated protein Srv2p, the RasGEF Cdc25p, and either of the RAS GTPases Ras1p or Ras2p (9, 10, 11, 12). Cyr1p activation is dependent upon its localization to the plasma membrane, a peripheral association that requires the RasGAP Ira1p (13). Cyr1p contains five domains: an N-terminal region of as yet unknown function, a Ras-binding region, a linker domain, a catalytic domain, and a C-terminal Srv2p-binding domain (10 and references therein).
Loss of Cyr1p activity leads to a decrease in the intracellular levels of cAMP, resulting in pleiotropic phenotypes that mimic nutrient starvation, such as growth arrest in the G1 phase of the cell cycle, increased life-span, and defects in sporulation, conjugation, and utilization of nonfermentable carbon sources (1, 14, 15, 16). cyr1 mutants are also more freeze tolerant and more resistant to certain types of stresses such as heat shock and oxidative stress (16, 17, and reviewed in 18).
Adenylate cyclases can be found in organisms ranging from bacteria to humans (19). Although the adenylate cyclases from E. coli and S. cerevisiae are able to functionally complement each other, the lack of amino acid similarity between these enzymes leads to the speculation that cAMP synthesis in prokaryotes and eukaryotes is an example of evolutionary convergence (20).
Last updated: 2007-06-07