YEAST PKA REPRESSES MSN2P MSN4P-DEPENDENT GENE-EXPRESSION TO REGULATEGROWTH, STRESS-RESPONSE AND GLYCOGEN ACCUMULATION/

Yeast cAMP-dependent protein kinase (PKA) activity is essential for gr owth and antagonizes induction of the general stress response as well as accumulation of glycogen stores. Previous studies have suggested th at the PKA effects on the two latter processes result in part from tra nscription repression. Here we show that transcription derepression th at accompanies PKU depletion is dependent upon the presence of two red undant Zn2+-finger transcription factors, Msn2p and Msn4p. The Msn2p a nd Msn4p proteins were shown previously to act as positive transcripti onal factors in the stress response pathway, and our results suggest t hat Msn2p and Msn4p also mediate PKA-dependent effects on stress respo nse as well as glycogen accumulation genes. Interestingly, PKA activit y is dispensable in a strain lacking Msn2p and Msn4p activity, Thus, M sn2p and Msn4p may antagonize PKA-dependent growth by stimulating expr ession of genes that inhibit growth, In agreement with this model, Msn 2p/pMsn4p function is required for expression of a gene, YAK1, previou sly shown to antagonize PKA-dependent growth, These results suggest th at Msn2p/Msn4p-dependent gene expression may account for all, or at le ast most, of the pleiotropic effects of yeast PKA, including growth re gulation, response to stress and carbohydrate store accumulation.