Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae

In response to various stresses, as well as during the diauxic transition, the Msn2p and Msn4p transcription factors of Saccharomyces cerevisiae are a ctivated and induce a large set of genes. This activation is inhibited by t he Ras/cAMP/PKA (cAMP-dependent protein kinase) pathway. Here we show by im munoblotting experiments that Msn2p and Msn4p are phosphorylated in vivo du ring growth on glucose, and become hyperphosphorylated at the diauxic trans ition and upon heat shock. This hyperphosphorylation is correlated with act ivation of Msn2/4p-dependent transcription. An increased level of cAMP prev ents and reverses these hyperphosphorylations. indicating that kinases othe r than PKA are involved. These results suggest that PKA and stress-activate d kinases control Msn2/4p activity by antagonistic phosphorylation. it was also noted that Msn4p is transiently increased at the diauxic transition. M sn2p and Msn4p present different hyperphosphorylation patterns in response to different stresses.