Cell Signaling & Neuroscience Glucocorticoid Receptor Signaling

Slides Programmed Cell Death Activation and Inhibition of Apoptosis Mitochondria in Apoptosis ATM/p53 Signaling Pathway Caspase Cascade Caspase Activation Intrinsic Pathway Granzyme B FAS and Related Proteins Fas Signaling G1, and S Phases G2 and M Phases Regulatory Cascade The p53 Signaling Pathway Cytokines and Growth Factors Structures of Activin and Inhibin Structures of Chemokine Receptors Angiopoietins EGFR Signaling Pathway Transmembrane Precursors of EGF Possible Receptor Combos and Ligand Actions of Flt-3/Flk-2 Hedgehog and BMI1 IGF Regulation of Apoptosis IL-13 and IL-4 receptor IL-18 Production Neurotrophins and Their Receptors TrkA GDNF Family with Receptors PDGF Receptors and Actions TGF-beta Signaling BMP Signaling TNF Signaling TNF-α and TNF-β Proposed Balance Between TNF Superfamily Structure of Receptors VEGF Receptor and Ligands Prolactin Regulation Insulin Pathway Glucocorticoid Receptor Signaling Vascular Endothelial Cell Interactions Integrin Signaling in Cell Survival VEGF Receptor Signaling MMPs and Cytokines Events Leading to Angiogenesis Transcription Factors Nuclear Complex Targeting Jak/Stat Pathway STAT3 PPAR Formation of Nucleosomes DNA Compaction Early Response Events Cell Cycle Checkpoint Linkage between DNA Repair and Chromatin Modification Functions of WRN, BLM and MRE11 mRNP Transport Importinα - Importinβ Pathway Modular Structure of Transcription factors Transcription Activation by Nuclear Receptors Coupled RNA Splicing and Nuclear Export RNA Polyadenylation Mammalian mRNA Polyadenylation RNA Maturation Epigenetic Control Phosphorylation-driven Initiation-Elongation cAMP Metabolism cGMP Metabolism G-Protein Signaling T Cell Receptor B Cell Receptor Monovalent Ion Channels Activation/Inactivation Ligand-Gated Ion Channel Aquaporin Channel Structure Calcium Channel Structure Calcium Channel Pore Region Chloride Channel HCN Channel 2TM Potassium Channel Structure 6TM Potassium Channel Structure Sodium Channel Structure Sodium Channel Pore Region PTEN Pathway Lipids in Cell Signaling Inositol Phosphates Phosphatidic Acid Inositol Phospholipids ABC Transporters ABC-ATPases BSEP MRP1 β-Amyloid Plaques Notch Secretase Second Messenger Systems Limbic Reward Circuit Major Pathways in the CNS Endothelin Signaling NPY and Catecholamines Ascending Pain Pathway Modulation of Pain Transmission Mechanism of Action Fig. A Mechanism of Action Fig. B Drug Activation of Dopaminergic GABAB Receptor Oxidative Stress nNOS eNOS iNOS Nitric Oxide Proteasome/Ubiquitination Formation of Activated 20S Proteasome Ubiquitin Pathway MAP Kinase Cascades AKT Signaling Pathways Activated by VEGF

Glucocorticoid Receptor Signaling

The glucocorticoid hormone, cortisol, passes through the plasma membrane into the cytoplasm where it binds to the specific, high-affinity glucocorticoid receptor (GR). The resulting complex is the non-DNA-binding oligomer of the GR, in which the receptor is complexed with other proteins. In this complex, the DNA-binding domain of the receptor is bound by the heat shock protein 90 (hsp90) dimer. Other proteins in this complex include heat shock protein 70 (hsp70) and FKBP52. Dissociation of the oligomeric complex yields the free cortisol-receptor subunit in the DNA-binding form. The activated receptor forms a homodimer and is translocated to the nucleus through the nucleopore. Inside the nucleus, the receptor complex binds to specific DNA responsive elements (GRE) to activate gene transcription.

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References:

Bruner, K.L., et al., The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. Recept. Signal Transduct., 7, 85-98 (1997).

Drouin, J., et al., Homodimer formation is rate-limiting for high affinity DNA binding by glucocorticoid receptor. Mol Endocrinol., 6, 1299-1309 (1992).