Integration of cell cycle signals by multi-PAS domain kinases.
Proc Natl Acad Sci U S A
; 115(30): E7166-E7173, 2018 07 24.
Article
en En
| MEDLINE
| ID: mdl-29987042
ABSTRACT
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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
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Proteínas Bacterianas
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Caulobacter crescentus
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Multimerización de Proteína
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article