Intermolecular relations between the glucocorticoid receptor, ZAP-70 kinase, and Hsp-90

Biochem Biophys Res Commun. 2007 Mar 2;354(1):253-8. doi: 10.1016/j.bbrc.2006.12.211. Epub 2007 Jan 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HSP90 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Protein Binding
  • Receptors, Glucocorticoid / metabolism*
  • Subcellular Fractions / metabolism*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism*


  • HSP90 Heat-Shock Proteins
  • Receptors, Glucocorticoid
  • ZAP-70 Protein-Tyrosine Kinase