title: Inactivation of SRC family tyrosine kinases by reactive oxygen species in vivo.
abstract: Reactive oxygen species, including H2O2, O2*- and OH* are constantly produced in the human body and are involved in the development of cardiovascular diseases. Emerging evidence suggests that reactive oxygen species, besides their deleterious effects at high concentrations, may be protective. However, the mechanism underlying the protective effects of reactive oxygen species is not clear. Here, we reported a novel finding that H2O2 at low to moderate concentrations (50-250 microM) markedly inactivated Src family tyrosine kinases temporally and spatially in vivo but not in vitro. We further showed that Src family kinases localized to focal adhesions and the plasma membrane were rapidly and permanently inactivated by H2O2, which resulted from a profound reduction in phosphorylation of the conserved tyrosine residue at the activation loop. Interestingly, the cytoplasmic Src family kinases were activated gradually by H2O2, which partially compensated for the loss of total activities of Src family kinases but not their functions. Finally, H2O2 rendered endothelial cells resistant to growth factors and cytokines and protected the cells from inflammatory activation. Because Src family kinases play key roles in cell signaling, the rapid inactivation of Src family kinases by H2O2 may represent a novel mechanism for the protective effects of reactive oxygen species.
authors.affiliation: Department of Biochemistry, The University of Texas Health Center at Tyler, Tyler, Texas 75708, USA. hua.tang@uthct.edu
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Rutherford
authors.forename: Brad
authors.initials: B
authors.lastname: Low
authors.forename: Z Joe
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D017382:Reactive Oxygen Species; D014443:Tyrosine; D006861:Hydrogen Peroxide; D019061:src-Family Kinases