THE SCH9 PROTEIN-KINASE IN THE YEAST SACCHAROMYCES-CEREVISIAE CONTROLS CAPK ACTIVITY AND IS REQUIRED FOR NITROGEN ACTIVATION OF THE FERMENTABLE-GROWTH-MEDIUM-INDUCED (FGM) PATHWAY

In cells of the yeast Saccharomyces cerevisiae, trehalase activation, repression of CTT1 (catalase), SSA3 (Hsp7O) and other STRE-controlled genes, feedback inhibition of cAMP synthesis and to some extent induct ion of ribosomal protein genes is controlled by the Ras-adenylate cycl ase pathway and by the fermentable-growth-medium-induced pathway (FGM pathway). When derepressed cells are shifted from a non-fermentable ca rbon source to glucose, the Ras-adenylate cyclase pathway is transient ly activated while the FCM pathway triggers a more lasting activation of the same targets when the cells become glucose-repressed. Activatio n of the FGM pathway is not mediated by cAMP but requires catalytic ac tivity of cAMP-dependent protein kinase (cAPK; Tpk1, 2 or 3). This stu dy shows that elimination of Sch9, a protein kinase with homology to t he catalytic subunits of cAPK, affects ail target systems in derepress ed cells in a way consistent with higher activity of cAPK in vivo. In vitro measurements with trehalase and kemptide as substrates confirmed that elimination of Sch9 enhances cAPK activity about two-to threefol d, in both the absence and presence of cAMP. In vivo it similarly affe cted the basal and final level but not: the extent of the glucose-indu ced responses in derepressed cells. The reduction in growth rate cause d by deletion of SCH9 is unlikely to be responsible for the increase i n cAPK activity since reduction of growth rate generally leads to lowe r cAPK activity in yeast. On the other hand, deletion of SCH9 abolishe d the responses of the protein kinase A targets in glucose-repressed c ells. Re-addition of nitrogen to cells starved for nitrogen in the pre sence of glucose failed to trigger activation of trehalase, caused str ongly reduced and aberrant repression of CTT1 and SSA3, and failed to induce the upshift in RPL25 expression. From these results three concl usions can be drawn: (1) Sch9 either directly or indirectly reduces th e activity of protein kinase A; (2) Sch9 is not required for glucose-i nduced activation of the Rasadenylate cyclase pathway; and (3) Sch9 is required for nitrogen-induced activation of the FCM pathway. The latt er indicates that Sch9 might be the target of the FGM pathway rather t han cAPK itself.