DOI: 10.1073/pnas.1808543115
论文题名: Integration of cell cycle signals by multi-PAS domain kinases
作者: Mann T.H. ; Shapiro L.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2018
卷: 115, 期: 30 起始页码: E7166
结束页码: E7173
语种: 英语
英文关键词: Caulobacter
; Cell division
; Cell fate
; Kinase
; Signaling
Scopus关键词: cholecystokinin A receptor
; DivL protein
; liposome
; multiprotein complex
; phosphatase
; unclassified drug
; bacterial protein
; protein kinase
; Article
; catalysis
; cell cycle regulation
; cell interaction
; cellular distribution
; controlled study
; enzyme activity
; in vitro study
; nonhuman
; oligomerization
; polar body
; priority journal
; protein domain
; signal transduction
; spatiotemporal analysis
; stem cell niche
; Caulobacter vibrioides
; chemistry
; enzymology
; protein domain
; protein multimerization
; protein quaternary structure
; Bacterial Proteins
; Caulobacter crescentus
; Protein Domains
; Protein Kinases
; Protein Multimerization
; Protein Structure, Quaternary
英文摘要: Spatial control of intracellular signaling relies on signaling proteins sensing their subcellular environment. In many cases, a large number of upstream signals are funneled to a master regulator of cellular behavior, but it remains unclear how individual proteins can rapidly integrate a complex array of signals within the appropriate spatial niche within the cell. As a model for how subcellular spatial information can control signaling activity, we have reconstituted the cell pole-specific control of the master regulator kinase/phosphatase CckA from the asymmetrically dividing bacterium Caulobacter crescentus. CckA is active as a kinase only when it accumulates within a microdomain at the new cell pole, where it colocalizes with the pseudokinase DivL. Both proteins contain multiple PAS domains, a multifunctional class of sensory domains present across the kingdoms of life. Here, we show that CckA uses its PAS domains to integrate information from DivL and its own oligomerization state to control the balance of its kinase and phosphatase activities. We reconstituted the DivL–CckA complex on liposomes in vitro and found that DivL directly controls the CckA kinase/phosphatase switch, and that stimulation of either CckA catalytic activity depends on the second of its two PAS domains. We further show that CckA oligomerizes through a multidomain interaction that is critical for stimulation of kinase activity by DivL, while DivL stimulation of CckA phosphatase activity is independent of CckA homooligomerization. Our results broadly demonstrate how signaling factors can leverage information from their subcellular niche to drive spatiotemporal control of cell signaling. © 2018 National Academy of Sciences. All Rights Reserved. Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163684
Appears in Collections: 气候变化与战略
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作者单位: Mann, T.H., Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Shapiro, L., Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, United States, Chan Zuckerberg Biohub, San Francisco, CA 94158, United States
Recommended Citation:
Mann T.H.,Shapiro L.. Integration of cell cycle signals by multi-PAS domain kinases[J]. Proceedings of the National Academy of Sciences of the United States of America,2018-01-01,115(30)