학술논문

Growth-Dependent Activation of Protein Kinases Suggests a Mechanism for Measuring Cell Growth
Document Type
article
Source
Genetics. 215(3)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
1.1 Normal biological development and functioning
Underpinning research
Generic health relevance
Cyclin-Dependent Kinases
Mitosis
Phospholipids
Phosphorylation
Protein Serine-Threonine Kinases
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
cell cycle
cell growth
cell size
Gin4
Hsl1
Developmental Biology
Biochemistry and cell biology
Language
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 function 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.