title: Src phosphorylation of cortactin enhances actin assembly.
abstract: Src kinase mediates growth factor signaling and causes oncogenic transformation, which includes dramatic changes in the actin cytoskeleton, cell shape, and motility. Cortactin was discovered as a substrate for Src. How phosphorylation of cortactin can enhance actin assembly is unknown. Here, using an actin assembly system reconstituted from purified components, we demonstrate for the first time a biochemical mechanism by which Src phosphorylation of cortactin affects actin assembly. The adaptor Nck is an important component of the system, linking phosphorylated cortactin with neuronal WASp (N-WASp) and WASp-interacting protein (WIP) to activate Arp2/3 complex.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. tehranis@medicine.wustl.edu
authors.forename: Shandiz
authors.initials: S
authors.lastname: Tehrani
authors.forename: Nenad
authors.initials: N
authors.lastname: Tomasevic
authors.forename: Scott
authors.initials: S
authors.lastname: Weed
authors.forename: Roman
authors.initials: R
authors.lastname: Sakowicz
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D051356:Cortactin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D013552:Swine; D014443:Tyrosine / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051356:Cortactin; C078332:Nck protein; D015513:Oncogene Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)