Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast

摘要: Abstract Background: In animal cells, recruitment of phosphatidylinositol 3-kinase by growth factor receptors generates 3-phosphoinositides, which stimulate 3-phosphoinositide-dependent protein kinase-1 (PDK1). Activated PDK1 then phosphorylates and activates downstream kinases, including kinase B (PKB)/c-Akt, p70 S6 kinase, PKC isoforms, serum- glucocorticoid-inducible (SGK), thereby eliciting physiological responses. Results: We found that two previously uncharacterised genes Saccharomyces cerevisiae , we term PKH1 PKH2 encode kinases with catalytic domains closely resembling those human Drosophila PDK1. Both Pkh1 Pkh2 were essential for cell viability. Expression in otherwise inviable pkh1 Δ pkh2 cells permitted growth. addition, the yeast YPK1 YKR2 to each a domain SGK; both Ypk1 Ykr2 also Otherwise ypk1 ykr2 fully rescued expression rat SGK, but not mouse PKB or kinase. Purified activated mammalian SGK PKBα vitro phosphorylating same residue as purified equivalent (Thr504) was required maximal phosphorylation vivo . Unlike PKB, activation did require 3,4,5-trisphosphate, consistent absence pleckstrin homology these proteins. The consensus sequence similar SGK. Conclusions: function similarly PDK1, As groups constitute tiers signalling cascade