title: Src redox regulation: there is more than meets the eye.
abstract: Src-family kinases are critically involved in the control of cytoskeleton organization and in the generation of integrin-dependent signaling responses, inducing tyrosine phosphorylation of many signaling and cytoskeletal proteins. Activity of the Src family of tyrosine kinases is tightly controlled by inhibitory phosphorylation of a carboxy-terminal tyrosine residue, inducing an inactive conformation through binding with its SH2 domain. Dephosphorylation of C-ter tyrosine, as well as its deletion of substitution with phenylalanine in oncogenic Src kinases, leads to autophosphorylation at a tyrosine in the activation loop, thereby leading to enhanced Src activity. Beside this phophorylation/dephosphorylation circuitry, cysteine oxidation has been recently reported as a further mechanism of enzyme activation. Mounting evidence describes Src activation via its redox regulation as a key outcome in several circumstances, including growth factor and cytokines signaling, integrin-mediated cell adhesion and motility, membrane receptor cross-talk as well in cell transformation and tumor progression. Among the plethora of data involving Src kinase in physiological and pathophysiological processes, this review will give emphasis to the redox component of the regulation of this master kinase.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Centre for Research, Transfer and High Education Study at Molecular and Clinical Level of Chronic Disorders for the Development on Novel Therapies, Firenze, Italy. paola.chiarugi@unifi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D019061:src-Family Kinases