Fig. 3.

GC signaling downstream of GR. A) GCs bind to intracellular nuclear receptors (GR, but also MR) to activate or repress transcription. GCs diffuse through the cell membrane and bind to cytoplasmic receptors (GR). This binding mediates dissociation of GR from heat shock proteins (hsp) and dimerization of GR molecules bound to GC. GR/GC complexes translocate into the nucleus where they bind to (negative) glucocorticoid response promoter elements ((n)GRE) and activate transcription or they bind to nGRE, leading to transrepression. Alternatively, they associate with other transcription factors (TF) and influence their action on corresponding responsive DNA elements (RE). B) Via non-classical signaling, GR dimers can also directly modify the activity of kinases such as phospho-inositol 3 kinase (PI3K), AKT, or mitogen activated protein kinase (MAPK), independent of genomic events.