title: p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate.
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.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Ratna K
authors.initials: RK
authors.lastname: Vadlamudi
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barnes
authors.forename: Rozita
authors.initials: R
authors.lastname: Bagheri-Yarmand
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D015723:Gene Library; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010590:Phalloidine / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology; D054462:p21-Activated Kinases
chemical_list: C460821:ARPC1B protein, human; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D010590:Phalloidine; D013912:Threonine; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases