TY - JOUR
T1 - Chemical genetics of AGC-kinases reveals shared targets of Ypk1, protein kinase A and Sch9
AU - Plank, Michael
AU - Perepelkina, Mariya
AU - Müller, Markus
AU - Vaga, Stefania
AU - Zou, Xiaoming
AU - Bourgoint, Clélia
AU - Berti, Marina
AU - Saarbach, Jacques
AU - Haesendonckx, Steven
AU - Winssinger, Nicolas
AU - Aebersold, Ruedi
AU - Loewith, Robbie
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases.
AB - Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases.
UR - http://www.scopus.com/inward/record.url?scp=85082777616&partnerID=8YFLogxK
U2 - 10.1074/mcp.RA120.001955
DO - 10.1074/mcp.RA120.001955
M3 - Article
C2 - 32102971
AN - SCOPUS:85082777616
SN - 1535-9476
VL - 19
SP - 655
EP - 671
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 4
ER -