title: FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly.
abstract: Cell migration is a complex, highly regulated process that involves the continuous formation and disassembly of adhesions (adhesion turnover). Adhesion formation takes place at the leading edge of protrusions, whereas disassembly occurs both at the cell rear and at the base of protrusions. Despite the importance of these processes in migration, the mechanisms that regulate adhesion formation and disassembly remain largely unknown. Here we develop quantitative assays to measure the rate of incorporation of molecules into adhesions and the departure of these proteins from adhesions. Using these assays, we show that kinases and adaptor molecules, including focal adhesion kinase (FAK), Src, p130CAS, paxillin, extracellular signal-regulated kinase (ERK) and myosin light-chain kinase (MLCK) are critical for adhesion turnover at the cell front, a process central to migration.
authors.affiliation: Department of Cell Biology, UVA School of Medicine, P.O. Box 800732, Charlottesville, Virginia 22908-0732, USA. djw2p@virginia.edu
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Webb
authors.forename: Karen
authors.initials: K
authors.lastname: Donais
authors.forename: Leanna A
authors.initials: LA
authors.lastname: Whitmore
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Thomas
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Turner
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Parsons
authors.forename: Alan F
authors.initials: AF
authors.lastname: Horwitz
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; C496062:Pxn protein, mouse; D011993:Recombinant Fusion Proteins; D050717:Retinoblastoma-Like Protein p130; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases; D009219:Myosin-Light-Chain Kinase; D020928:Mitogen-Activated Protein Kinases