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RESEARCH PRODUCT
SIK2 orchestrates actin-dependent host response upon Salmonella infection
Keith B. BoyleChunaram ChoudharyIvan DikicAdriana Covarrubias-pintoMarcel HahnShankha SatpathyKevin KlannFelix RandowChristian MünchLina HerhausKrishnaraj Rajalingamsubject
ProteomicsSalmonellaactin cytoskeletonImmunoblottingArp2/3 complexSalmonella infectionmacromolecular substancesProtein Serine-Threonine Kinasesmedicine.disease_causeBiochemistry03 medical and health sciencesMice0302 clinical medicineSalmonellamedicineXenophagyAnimalsHumansArp2/3 complexProtein Interaction MapsPhosphorylationActinCells Cultured030304 developmental biologyActin nucleation0303 health sciencesMultidisciplinarybiologyEpithelial CellsBiological Sciencesmedicine.diseaseActin cytoskeletonHCT116 CellsPhosphoproteinsActinsCell biologySalmonella-containing vacuoleHEK293 CellsFormins407Host-Pathogen Interactionsbiology.proteinRNA Interference030217 neurology & neurosurgeryhost–pathogen interactionsHeLa CellsSignal Transductiondescription
Significance Through conducting quantitative proteomics upon Salmonella infection, we identified a SIK2 signaling network, implementing the kinase into a so far concealed biological function. Our data exposed SIK2 as a central orchestrator of an actin regulatory network, coordinating the stability of Salmonella-containing vacuole (SCV) and cellular actin assembly, in order to limit the acute phase of the infection. Most strikingly, SIK2 is not exclusively acting locally on actin assembly associated with the SCV but impacts the actin cytoskeleton architecture in its entirety upon Salmonella infection. Our work provides a mechanistic framework for how the actin cytoskeleton is regulated and how it helps to control an acute Salmonella infection.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-01 | Proceedings of the National Academy of Sciences of the United States of America |