PAS Kinase and TOR, Controllers of Cell Growth and Proliferation

• Main Author: Cozzens, Brooke Jasmyn
• Format: Others
• Published: BYU ScholarsArchive 2019
• Subjects: PAS kinase; gene duplication; mTOR; TORC1; TORC2; glucose metabolism; signal transduction; nutrient sensing; Direct Coupling Analysis; Ugp1; Cbf1; Utr1; USF1; ATXN2
• Online Access: https://scholarsarchive.byu.edu/etd/8127; https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=9127&context=etd

Nutrient sensing kinases lie at the heart of cellular health and homeostasis, allowing cells to quickly adapt to changing environments. Target of Rapamycin (TOR) and PAS kinase (PASK, or PASKIN) are two such nutrient kinases, conserved from yeast to man. In yeast, these kinases each have paralogs. The two TOR paralogs in yeast mimic the mammalian TORC1 and TORC2 complexes, except both Tor1 and Tor2 may contribute to TORC1 or TORC2 function. The two PAS kinase paralogs are paired with the TOR paralogs, meaning that both Psk1 and Psk2 regulate TORC1, while Psk2 suppresses a temperature-sensitive allele of Tor2. Herein we review the evolutionary models for these paralogs, their function in yeast and mammalian cells, as well as the overlapping function of PAS kinase and TOR. We also use Rice University’s Direct Coupling Analysis algorithms to analyze co-evolutionary relationships and identify potential interaction sites between PAS kinase and several of its substrates.