title: Intermolecular relations between the glucocorticoid receptor, ZAP-70 kinase, and Hsp-90.
abstract: The glucocorticoid receptor (GR) participates in both genomic and non-genomic glucocorticoid hormone (GC) actions by interacting with other cytoplasmic signalling proteins. Previously, we have shown that high dose Dexamethasone (DX) treatment of Jurkat cells causes tyrosine phosphorylation of ZAP-70 within 5 min in a GR-dependent manner. By using co-immunoprecipitation and confocal microscopy, here we demonstrate that the liganded GR physically associates with ZAP-70, in addition to its phosphorylation changes. The association of the ligand-bound GR and ZAP-70 was also observed in HeLa cells transfected with ZAP-70, suggesting that this co-clustering is independent of lymphocyte specific factors. Furthermore, the ZAP-70 was found to also co-precipitate with Hsp-90 chaperone both in Jurkat and transgenic HeLa cells, independent of the presence of DX. These findings raise the possibility that ZAP-70 may serve as an important link between GC and TcR-induced signaling, thereby transmitting non-genomic GC action in T-cells.
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, Hungary. dominicus@freemail.hu
authors.forename: Domokos
authors.initials: D
authors.lastname: Bartis
authors.forename: Ferenc
authors.initials: F
authors.lastname: Boldizsár
authors.forename: Krisztián
authors.initials: K
authors.lastname: Kvell
authors.forename: Mariann
authors.initials: M
authors.lastname: Szabó
authors.forename: László
authors.initials: L
authors.lastname: Pálinkás
authors.forename: Péter
authors.initials: P
authors.lastname: Németh
authors.forename: Eva
authors.initials: E
authors.lastname: Monostori
authors.forename: Tímea
authors.initials: T
authors.lastname: Berki
mesh_terms: D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D051746:ZAP-70 Protein-Tyrosine Kinase