Growth-dependent activation of protein kinases links cell cycle progression to cell growth

Abstract

In all cells, progression through the cell cycle occurs only when sufficient growth has occurred. Thus, cells must translate growth into a proportional signal that can be used to measure and transmit information about growth. Previous genetic studies in budding yeast suggested that related kinases called Gin4 and Hsl1 could play roles in mechanisms that measure bud growth; however, interpretation of the data was complicated by the use of gene deletions that cause complex terminal phenotypes. Here, we used the first conditional alleles of Gin4 and Hsl1 to more precisely define their functions. We show that excessive bud growth during a prolonged mitotic delay is an immediate consequence of inactivating Gin4 and Hsl1. Thus, acute loss of Gin4 and Hsl1 causes cells to behave as though they cannot detect that bud growth has occurred. We further show that Gin4 and Hsl1 undergo gradual hyperphosphorylation during bud growth that is dependent upon growth and correlated with the extent of growth. Moreover, gradual hyperphosphorylation of Gin4 during bud growth requires binding to anionic phospholipids that are delivered to the growing bud. While alternative models are possible, the data suggest that signaling lipids delivered to the growing bud generate a growth-dependent signal that could be used to measure bud growth.