title: c-Src and HSP72 interact in ATP-depleted renal epithelial cells.
abstract: Disruption of cell contact sites during ischemia contributes to the loss of organ function in acute renal failure. Because prior heat stress protects cell contact sites in ATP-depleted renal epithelial cells in vitro, we hypothesized that heat shock protein 72 (HSP72), the major inducible cytoprotectant in mammalian cells, interacts with protein kinases that regulate cell-cell and cell-matrix interactions. ATP depletion increased the content of Tyr(416) Src, the activated form of this kinase. c-Src activation was associated with an increase in the tyrosine phosphorylation state of beta-catenin, paxillin, and vinculin, three c-Src substrate proteins that localize to and regulate cell contact sites. Prior heat stress inhibited c-Src activation and decreased the degree of tyrosine phosphorylation of all three Src substrates during ATP depletion and/or early recovery. HSP72 coimmunoprecipitated with c-Src only in cells subjected to heat stress. ATP depletion markedly increased the interaction between HSP72 and c-Src, supporting the hypothesis that HSP72 regulates Src kinase activity. These results suggest that alterations in the tyrosine phosphorylation state of proteins located at the cell-cell and cell-matrix interface mediate, at least in part, the functional state of these structures during ATP depletion and may be modulated by interactions between HSP72 and c-Src.
authors.affiliation: Department of Pathology, School of Medicine, Tufts University and New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.forename: J H
authors.initials: JH
authors.lastname: Schwartz
authors.forename: P J
authors.initials: PJ
authors.lastname: Flint
authors.forename: S C
authors.initials: SC
authors.lastname: Borkan
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006358:Hot Temperature; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D009893:Opossums; D010766:Phosphorylation; D011092:Polyethylene Glycols; D011233:Precipitin Tests; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011092:Polyethylene Glycols; D014443:Tyrosine; D000255:Adenosine Triphosphate; D019061:src-Family Kinases