title: Src-dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complex.
abstract: The WAVE/Scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the Arp2/3 complex in response to extracellular cues. Within cells they form part of a pentameric complex that is thought to regulate their ability to interact and activate the Arp2/3 complex. However, the exact mechanism for this is not known. We set out to assess whether phosphorylation of Scar1 by the non-receptor tyrosine kinase Src may influence the function of Scar1 and its ability to regulate Arp2/3-mediated actin polymerisation. We show that Scar1 is phosphorylated by Src in vitro and in vivo and identify tyrosine 125 as the major site in Scar1 to be phosphorylated in cells. Src-dependent phosphorylation of Scar1 on tyrosine 125 enhances its ability to bind to the Arp2/3 complex and regulates its ability to control actin polymerisation in cells. Thus, Src may act as an intermediary to regulate the activity of the Arp2/3 complex in response to external stimuli, via modulation of its interaction with WAVE/Scar proteins.
authors.affiliation: The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Bearsden, Glasgow G61 1BD, United Kingdom.
authors.forename: Hazel
authors.initials: H
authors.lastname: Ardern
authors.forename: Emma
authors.initials: E
authors.lastname: Sandilands
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Brunton
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D010766:Phosphorylation; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D019061:src-Family Kinases