Standard model of the Ras/cAMP/PKA/Msn2/4 pathway.

Under benign, glucose-replete conditions, the GTPases Ras1 and Ras2 exist predominantly in their GTP-bound form, which stimulates activity of the adenylyl cyclase Cyr1, thereby increasing intracellular cAMP concentration. Under glucose starvation, intracellular cAMP concentration decreases by virtue of the countervailing effects of the GTPase-activating proteins Ira1 and Ira2, which cause Ras1 and Ras2 to exist predominantly in their GDP-bound form, and the phosphodiesterases Pde1 and Pde2, which convert cAMP to AMP. Ira1 and Ira2 also positively regulate phosphoinositol metabolism independent of the Ras/cAMP pathway. cAMP activates PKA by relieving the inhibitory effect of Bcy1 (not shown). PKA phosphorylates both Msn2 and Msn4. The effect on Msn2 is to decrease its nuclear import and increase its nuclear export, rendering it less likely to activate its target genes, one of which is Msn4. Msn2 and Msn4 both repress cell growth and activate the stress response, but are not completely redundant and are therefore shown as regulating partially overlapping sets of stress-response target genes. See text for more details.