title: Src redox regulation: again in the front line.
abstract: Src-family kinases are vitally important to the regulation of cytoskeleton organization, cell proliferation, and the generation of integrin-dependent signaling responses, inducing tyrosine phosphorylation of many signaling and cytoskeletal proteins. The activity of the Src kinase is tightly controlled by inhibitory phosphorylation of a carboxy-terminal tyrosine residue, of which dephosphorylation, or deletion/substitution with phenylalanine in oncogenic Src kinases, leads to enhanced Src activity owing to autophosphorylation in the activation loop. Alongside this phosphorylation/dephosphorylation control, cysteine oxidation has been recently reported as a further mechanism of enzyme activation. Increasing evidence describes redox regulation of Src kinase as a key outcome in growth factor and cytokine signaling, integrin-mediated cell adhesion and motility, and membrane receptor cross talk, as well as in cell transformation, tumor progression, and metastatic dissemination. Src kinase is also involved in the regulation of localized ROS production at invadopodia and podosomes, subcellular adhesion structures associated with extracellular matrix degradation, through spatially restricted activation of NADPH oxidase. Therefore Src kinase both affects and is affected by oxidative signaling, thereby allowing the fine-tuning of the multifaceted cytoskeleton responses for motility and invasion.
authors.affiliation: Department of Biochemical Sciences, Tuscany Tumor Institute, and Center for Research, Transfer, and High Education DenoTHE, University of Florence, 50134 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannoni
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Taddei
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
mesh_terms: D003599:Cytoskeleton / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D019061:src-Family Kinases