The human androgen receptor gene in the androgen sensitive prostate tumor cell line (LNCaP) contains a point mutation in codon 868 resulting in the substitution of threonine by alanine. This amino acid change is responsible for the increased affinity of the mutant receptor protein for progestagens and estrogens. To further elucidate the role of threonine 868 on androgen binding capacity, specificity and functional activity, threonine 868 was substituted by six different amino acid residues. Substitution by aspartic acid, lysine or tyrosine totally eliminated androgen binding and the mutated androgen receptors did not have any transcriptional activating potential with either R1881, R5020 or estradiol. Introduction of a serine or an alanine broadened the steroid specificity, as did the introduction of a cysteine to a lesser degree. It is concluded that threonine on position 868 of the human androgen receptor limits the ligand specificity of the receptor to androgens.

Additional Metadata
Persistent URL dx.doi.org/10.1006/bbrc.1993.2231, hdl.handle.net/1765/57560
Journal Biochemical and Biophysical Research Communications
Citation
Ris-Stalpers, C, Verleun-Mooijman, M.C, Trapman, J, & Brinkmann, A.O. (1993). Threonine on amino acid position 868 in the human androgen receptor is essential for androgen binding specificity and functioanl activity. Biochemical and Biophysical Research Communications, 196(1), 173–180. doi:10.1006/bbrc.1993.2231