title: Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells.
abstract: Hyperthermia adversely affects cell structure and function, but also induces adaptive responses that allow cells to tolerate these stressful conditions. For example, heat-induced expression of the molecular chaperone protein HSP70 can prevent stress-induced cell death by inhibiting signaling pathways that lead to apoptosis. In this study, we used high-resolution two-dimensional gel electrophoresis and phosphoprotein staining to identify signaling pathways that are altered by hyperthermia and modulated by HSP70 expression. We found that in heat-shocked cells, the actin-severing protein cofilin acquires inhibitory Ser3 phosphorylation, which is associated with an inhibition of chemokine-stimulated cell migration. Cofilin phosphorylation appeared to occur as a result of the heat-induced insolubilization of the cofilin phosphatase slingshot (SSH1-L). Overexpression of HSP70 reduced the extent of SSH1-L insolubilization and accelerated its resolubilization when cells were returned to 37°C after exposure to hyperthermia, resulting in a more rapid dephosphorylation of cofilin. Cells overexpressing HSP70 also had an increased ability to undergo chemotaxis following exposure to hyperthermia. These results identify a critical heat-sensitive target controlling cell migration that is regulated by HSP70 and point to a role for HSP70 in immune cell functions that depend upon the proper control of actin dynamics.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Jodie P
authors.initials: JP
authors.lastname: Simard
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Reynolds
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kraguljac
authors.forename: Graham S T
authors.initials: GS
authors.lastname: Smith
authors.forename: Dick D
authors.initials: DD
authors.lastname: Mosser
mesh_terms: D051339:Actin Depolymerizing Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D051339:Actin Depolymerizing Factors; D018840:HSP70 Heat-Shock Proteins; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human