Abstract
The formation of new branched actin filament networks at the cell cortex of migrating cells is choreographed by the actin-related protein (Arp) 2/3 complex. Despite the fundamental role of the Arp2/3 complex in actin nucleation and branching, upstream signals that control the functions of p41-Arc, a putative regulatory component of the mammalian Arp2/3 complex, remain unidentified. Here we show that p41-Arc interacts with p21-activated kinase 1 (Pak1) both in vitro and in vivo. Pak1 phosphorylation of p41-Arc regulates its localization with the Arp2/3 complex in the cortical nucleation regions of cells. Pak1 phosphorylates p41-Arc on threonine 21 in the first WD repeat, and its mutation has functional implications in vivo. Threonine 21 phosphorylation by Pak1 is required for both constitutive and growth-factor-induced cell motility. Pak1 regulation of p41-Arc activation status represents a novel mechanism by which signalling pathways may influence the functions of the Arp2/3 complex, leading to motility in mammalian cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / metabolism
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Actin-Related Protein 2-3 Complex
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Actins / chemistry
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Actins / genetics
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Actins / metabolism*
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Cell Movement / drug effects
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Cell Movement / physiology*
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Epidermal Growth Factor / metabolism
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Epidermal Growth Factor / pharmacology
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Gene Library
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Glutathione Transferase / analysis
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Humans
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Immunoprecipitation
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Mutation / genetics
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Mutation / physiology
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Phalloidine / chemistry
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / metabolism*
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Protein Subunits / genetics
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Protein Subunits / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / pharmacology
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Threonine / genetics
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Threonine / metabolism
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Wound Healing / physiology
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p21-Activated Kinases
Substances
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ARPC1B protein, human
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Actin-Related Protein 2-3 Complex
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Actins
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Protein Subunits
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RNA, Small Interfering
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Phalloidine
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Threonine
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Epidermal Growth Factor
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Glutathione Transferase
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PAK1 protein, human
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Protein Serine-Threonine Kinases
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p21-Activated Kinases