Mutations in squirrel monkey glucocorticoid receptor impair nuclear translocation. Academic Article uri icon

Overview

abstract

  • To identify the determinants of impaired glucocorticoid receptor (GR) signaling in a model of glucocorticoid resistance, cloned GR from Guyanese squirrel monkeys (gsmGR) was tagged with enhanced green fluorescent protein, and nuclear translocation was examined in transfected COS1 cells. In keeping with evidence that gsmGR transactivational competence is impaired, we found that nuclear translocation is likewise diminished in gsmGR relative to human GR (hGR). Experiments with GR chimeras revealed that replacement of the gsmGR ligand binding domain (LBD) with that from hGR increased translocation. Truncated gsmGR constructs lacking the LDB after amino acid 552 also showed increased translocation even in the absence of cortisol. Three back-mutations of gsmGR to hGR (Thr551Ser, Ala616Ser, and Ser618Ala) in the LBD confirmed that these amino acids play a role in diminished translocation.

publication date

  • February 24, 2005

Research

keywords

  • Receptors, Glucocorticoid
  • Saimiri
  • Translocation, Genetic

Identity

Scopus Document Identifier

  • 18044366012

Digital Object Identifier (DOI)

  • 10.1016/j.jsbmb.2004.11.010

PubMed ID

  • 15857751

Additional Document Info

volume

  • 94

issue

  • 4