Skip to Content
Merck
  • Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles.

Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles.

Molecular and cellular biology (2008-10-08)
Amy Jo Galliher-Beckley, Jason Grant Williams, Jennifer Brady Collins, John Anthony Cidlowski
ABSTRACT

Aberrant glycogen synthase kinase 3beta (GSK-3beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). Glucocorticoid signaling is essential for life and regulates diverse biological functions from cell growth to metabolism to apoptosis. Specifically, we found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta. Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. Furthermore, GSK-3beta-mediated GR phosphorylation inhibited glucocorticoid-dependent NF-kappaB transrepression and attenuated the glucocorticoid-dependent cell death of osteoblasts. Collectively, our results describe a novel convergence point of the GSK-3beta and the GR pathways, resulting in altered hormone-regulated signaling. Our results also provide a mechanism by which GSK-3beta activity can dictate how cells will ultimately respond to glucocorticoids.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
AR-A014418, ≥98% (HPLC), solid
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, For pulsed field electrophoresis running gel
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, BioReagent, for molecular biology, low EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Low EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, BioReagent, for molecular biology, Wide range/Standard 3:1
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Ultra-low Gelling Temperature, molecular biology grade
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Type IV, Special High EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, for molecular biology
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Type I-A, low EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, High EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Low EEO, for Immunoelectrophoresis
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Type I, low EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Ultra-low Gelling Temperature
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, High EEO, for molecular biology
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Special High EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Type II-A, Medium EEO
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Wide range, for molecular biology
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, High Gelling Temperature
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Agarose, Medium EEO, for molecular biology
SKU
Pack Size
Availability
Price
Quantity