Mechanism Of CAMP Signaling And Chronological Aging In The Yeast Saccharomyces Cerevisiae

In the yeast Saccharomyces cerevisiae, the cAMP signaling pathway (the Ras/cAMP/PKA signal transduction pathway)plays very important roles in the control of metabolism, proliferation, differentiation and acquisition of stress resistance. During the last twenty years, this pathway has attracted a great deal of attention and has been studied both intensively and extensively. To date, many components of the pathway have been identified and preliminary knowledge about the function of the pathway and the nature of the signal transduced by the pathway has been obtained. However, many scientific questions concerning sinal transduction mechanism and physiological function of the pathway remain to be elucidated.This work focuses on the following issues: different functions of the two cAMP phosphodiesterases, Pde1 and Pde2, in the regulation of intracellular cAMP levels; the effects of Ras1 and Ras2 on cAMP synthesis; the requirement of nitrogen source and the Sch9 protein kinase in glucose-induced activation of the Ras-cAMP pathway; relations of the activity of the Ras-cAMP pathway, heat stress resistance and chronological aging.Our results indicate that in a PKA attenuated strain, Pde1 has little effect on the pathway compared to Pde2 and that, in addition to down-regulating glucose-induced cAMP signal through a feedback mechanism, Pde1 also plays an important role in the regulation of intracellular cAMP levels in cells growing into stationary phase.Deletion of the RAS1 or RAS2 gene has different effect on the Ras-cAMP pathway. Deletion of RAS1 has little effect on the activity of the pathway but deletion of RAS2 affects the pathway significantly. The different effect of the two RAS genes on the activity of the pathway is due to the different strength of their promoter governing transcription of each gene but not the encoded protein per se.Nitrogen is important for glucose sensing and hence glucose-induced activation of the Ras-cAMP pathway. In the presence of nitrogen, the Sch9 protein kinase positively regulates the activity of the pathway. Under nitrogen starvation conditions, however, Sch9 inhibits glucose-induced cAMP signaling. Apparently, Sch9 integrates nutritional information, i.e., the presence of both glucose and nitrogen source into cAMP signaling, to coordinate cell's biological activities.The chronological life span of yeast cells pregrown in glucose containing medium correlates reversely with the activities of the Ras-cAMP pathway and directly with the degrees of cell's ability to resist heat stress. On the other hand, when yeast cells were precultured in a medium containing a nonfermentable carbon source, the correlation of chronological life span with the activity of the Ras-cAMP pathway and the stress resistance is reversed, indicating that the Ras-cAMP pathway in yeast regulate longevity via different mechanisms under these two different conditions.