The Yeast Protein Kinase Sch9 Functions as a Central Nutrient-Responsive Hub That Calibrates Metabolic and Stress-Related Responses

Abstract

Yeast cells are equipped with different nutrient signaling pathways that enable them to sense the availability of various nutrients and adjust metabolism and growth accordingly. These pathways are part of an intricate network since most of them are cross-regulated and subject to feedback regulation at different levels. In yeast, a central role is played by Sch9, a protein kinase that functions as a proximal effector of the conserved growth-regulatory TORC1 complex to mediate information on the availability of free amino acids. However, recent studies established that Sch9 is more than a TORC1-effector as its activity is tuned by several other kinases. This allows Sch9 to function as an integrator that aligns different input signals to achieve accuracy in metabolic responses and stress-related molecular adaptations. In this review, we highlight the latest findings on the structure and regulation of Sch9, as well as its role as a nutrient-responsive hub that impacts on growth and longevity of yeast cells. Given that most key players impinging on Sch9 are well-conserved, we also discuss how studies on Sch9 can be instrumental to further elucidate mechanisms underpinning healthy aging in mammalians.