Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN.

ABSTRACT: Although glucocorticoid (GC)-induced nongenomic effects have been reported, the underlying mechanisms remain unexplained. We previously described that lymphocyte-specific protein tyrosine kinase (LCK) and FYN oncogene related to SRC, FGR, YES (FYN) mediate GC-induced inhibition of T-cell-receptor (TCR) signalling. Here we characterize the underlying molecular mechanism. The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation. Experiments with cells transfected with GC-receptor short interfering RNA (siRNA) showed that the GC receptor is an essential component of the TCR signalling complex. Short-term GC treatment induces dissociation of this protein

SUBMITTER: Lowenberg M 

PROVIDER: S-EPMC1618362 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature