Src phosphorylation of cortactin enhances actin assembly.
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.
Tehrani
Shandiz
S
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. tehranis@medicine.wustl.edu
Tomasevic
Nenad
N
Weed
Scott
S
Sakowicz
Roman
R
Cooper
John A
JA
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
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)