title: Extracellular heat shock protein 70 mediates heat stress-induced epidermal growth factor receptor transactivation in A431 carcinoma cells.
abstract: The initial steps of heat stress in A431 cells were previously characterized by ligand-independent EGFR transactivation via an unknown mechanism and concomitant secretion of Hsp70. In this work we demonstrate that the depletion of Hsp70 from the conditioned medium of heated cells abolishes EGFR transactivation indicating that secreted Hsp70 is essential for EGFR transactivation during heat shock. This notion is supported by the findings that purified Hsp70 can induce EGFR transactivation and the activation of EGFR-dependent signaling pathways. Both heat stress and pure Hsp70 stimulate activation of TLR2/4 and their association with EGFR. These results suggest that the secreted Hsp70 mediates the cross-communication of TLR and EGFR signaling systems in A431 cells.
authors.affiliation: Department of Cell Signaling and Transport, Institute of Cytology, RAS, 4 Tychoretsky av., S-Petersburg, Russia. evdonin@mail.ru
authors.forename: Anton L
authors.initials: AL
authors.lastname: Evdonin
authors.forename: Irina V
authors.initials: IV
authors.lastname: Guzhova
authors.forename: Boris A
authors.initials: BA
authors.lastname: Margulis
authors.forename: Natalia D
authors.initials: ND
authors.lastname: Medvedeva
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D002417:Cattle; D017077:Culture Media, Conditioned; D066246:ErbB Receptors / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology*; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D006979:Hyperthermia, Induced; D053614:Janus Kinase 2 / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D018840:HSP70 Heat-Shock Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019000:Phosphotyrosine; D066246:ErbB Receptors; D053614:Janus Kinase 2