Search results for "PAK1"

showing 2 items of 2 documents

Injured Axons Instruct Schwann Cells to Build Constricting Actin Spheres to Accelerate Axonal Disintegration

2019

Summary: After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin…

Male0301 basic medicineCellGeneral Biochemistry Genetics and Molecular BiologyCell LineMice03 medical and health sciences0302 clinical medicinePAK1Downregulation and upregulationPeripheral Nerve InjuriesmedicineAnimalsRats WistarAxonlcsh:QH301-705.5Cells CulturedActinPlacenta Growth FactorVascular Endothelial Growth Factor Receptor-1ChemistryActinsAxonsRatsCell biologyMice Inbred C57BLOligodendrogliaCrosstalk (biology)030104 developmental biologymedicine.anatomical_structurelcsh:Biology (General)p21-Activated Kinasesnervous systemcardiovascular systemNerve lesionFemaleSchwann Cells030217 neurology & neurosurgerySignal TransductionClearanceCell Reports
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Rac1 and PAK1 are upstream of IKK-ε and TBK-1 in the viral activation of interferon regulatory factor-3

2004

The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFN beta, which is mainly controlled by the IFN-regulatory factor-3 (IRF-3). The signaling pathways mediating viral IRF-3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF-3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFN beta promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF-3, we have identified the kinase p21-activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF-3 activators, I kappa B kinase- and TANK-binding kina…

rac1 GTP-Binding ProteinTranscription GeneticBiophysicsIκB kinaseProtein Serine-Threonine KinasesSignal transductionBiologyVirus ReplicationBiochemistryCell LineDogsPAK1Structural BiologyInterferonGeneticsmedicineAnimalsHumansPhosphorylationPromoter Regions Geneticp21-activated kinasesMolecular BiologyRNA Double-StrandedKinaseRho GTPaseI-Kappa-B KinaseNuclear ProteinsInterferon-betaCell BiologyCREB-Binding ProteinI-kappa B KinaseDNA-Binding ProteinsEnzyme Activationp21-Activated KinasesInfluenza A virusViral infectionAnti-viral responseTrans-ActivatorsCancer researchInterferon Regulatory Factor-3Transcription factorSignal transductionDimerizationTranscription FactorsInterferon regulatory factorsmedicine.drugFEBS Letters
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