p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate.
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.
Mesh Terms:
Actin-Related Protein 2-3 Complex, Actins, Cell Movement, Epidermal Growth Factor, Gene Library, Glutathione Transferase, Humans, Immunoprecipitation, Microfilaments, Mutation, Phalloidine, Phosphorylation, Protein Binding, Protein Subunits, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Threonine, Wound Healing, p21-Activated Kinases
Actin-Related Protein 2-3 Complex, Actins, Cell Movement, Epidermal Growth Factor, Gene Library, Glutathione Transferase, Humans, Immunoprecipitation, Microfilaments, Mutation, Phalloidine, Phosphorylation, Protein Binding, Protein Subunits, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Threonine, Wound Healing, p21-Activated Kinases
EMBO Rep.
Date: Feb. 01, 2004
PubMed ID: 14749719
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