Regulation of protein kinase A activity in yeast by the Sse1
molecular chaperone.
Amy Trott, Lance Shaner, Kevin Morano
Microbiol. and Molec. Gen., Univ. of Texas Med. School, 6431 Fannin St.,
Houston, TX 77030, USA
The Hsp90 chaperone system stabilizes and regulates critical signaling
proteins in eukaryotic cells. The Sch9 protein kinase has been
identified as a negative regulator of Hsp90 in yeast, but the mechanism
of regulation is unknown. To gain insight into the relationship between
Sch9 and Hsp90, we constructed yeast strains carrying double disruptions
of the SCH9 gene and genes encoding members of the Hsp90
chaperone complex. A synthetic temperature sensitive lethal interaction
was found between SCH9 and the yeast Hsp110 family member,
SSE1 , which participates in Hsp90 activities in vivo. A screen
for high copy suppressors of the temperature sensitive phenotype of an
sch9delta sse1delta strain identified both the IRA1 and
IRA2 genes. The IRA genes act as GTPase activating
proteins for the signaling protein Ras, and are therefore negative
regulators of Ras activation of adenylate cyclase. Overexpression of the
phosphodiesterase PDE2 or the inhibitory subunit of protein
kinase A (PKA), BCY1 , also suppresses the ts growth defect. The
general stress response pathway is strongly repressed and accumulation
of the storage carbohydrates glycogen and trehalose is greatly
diminished in sch9delta sse1delta cells. Together, these findings
suggest that PKA is hyperactive in these cells, and begin to define a
novel cellular role for the poorly understood Sse1 chaperone. We are
currently working to elucidate the links between PKA, Sch9 and the Hsp90
chaperone complex.
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