The Ras/PKA pathway controls gene expression by regulating the
activity of Srb complex proteins present in the RNA pol II
holoenzyme.
Ya-Wen Chang, Paul K. Herman
Molecular Genetics, The Ohio State University, 484 W.12th Ave.,
Columbus, OH 43210, USA
Upon nutrient deprivation, S. cerevisiae cells arrest division
and enter into a specialized resting state, known as stationary phase.
The entry into this resting state is regulated in part by the Ras/PKA
(cAMP-dependent protein kinase) signaling pathway. We are interested in
defining the targets of PKA relevant for this growth control. To this
end, we have identified a collection of rye mutants that are
defective in the transcriptional response to nutrient deprivation and in
stationary phase entry. Interestingly, three of these RYE genes
have been shown to encode the Srb/Ssn proteins, Srb9p, Srb10p, and
Srb11p. These Srb proteins are part of the Srb complex associated with
the RNA polymerase II holoenzyme. We found that specific transcription
defects associated with these srb mutations were suppressed by
RAS2val19, a hyperactive allele of RAS2.
However, increased Ras signaling was not able to correct the expression
defects associated with an srb9 null mutant suggesting that the
Srb9 protein is essential for the Ras suppression. Moreover, there are
two potential PKA sites in Srb9p, and our results show that the
suppression of the srb9 defects requires the presence of these
two PKA sites. In addition, Srb9p is a phosphoprotein in vivo,
and these two Srb9p sites are phosphorylated by PKA in vitro. In
all, our results suggest that Srb9p is a substrate for PKA, and this
phosphorylation of Srb9p modulates the in vivo activity of the
Srb complex.
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