title: Phosphorylation at Y1065 in vinculin mediates actin bundling, cell spreading, and mechanical responses to force.
abstract: Vinculin is an essential structural adaptor protein that localizes to sites of adhesion and is involved in a number of cell processes including adhesion, spreading, motility, force transduction, and cell survival. The C-terminal vinculin tail domain (Vt) contains the necessary structural components to bind and cross-link actin filaments. Actin binding to Vt induces a conformational change that promotes dimerization through the C-terminal hairpin of Vt and enables actin filament cross-linking. Here we show that Src phosphorylation of Y1065 within the C-terminal hairpin regulates Vt-mediated actin bundling and provide a detailed characterization of Y1065 mutations. Furthermore, we show that phosphorylation at Y1065 plays a role in cell spreading and the response to the application of mechanical force.
authors.affiliation: Department of Cell Biology and Physiology, ‡Department of Biochemistry and Biophysics, §Graduate Molecular and Cellular Biophysics Program, ∥Department of Physics and Astronomy, and ⊥the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Tolbert
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Richard
authors.initials: R
authors.lastname: Superfine
authors.forename: Keith
authors.initials: K
authors.lastname: Burridge
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Campbell
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D016596:Vinculin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D016596:Vinculin