Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors.
Two distinct v-erbA-related cDNA clones representing the products of different genes were isolated from a rat liver cDNA library. The first, rc-erbA-alpha, was 82% identical to v-erbA and encoded a polypeptide with a calculated molecular mass of 45,000 daltons. This cDNA clone arises from the same gene product as a v-erbA-related cDNA isolated from rat brain by Thompson et al. (Thompson, C. C., Weinberger, C., Lebo, R., and Evans, R. (1987) Science 237, 1610-1614). The second cDNA clone, rc-erbA-beta, was 76% identical to v-erbA and encoded a polypeptide with a calculated molecular mass of 52,000 daltons. Both rc-erbA-alpha and rc-erbA-beta translational products bound 3,5,3'-triiodo-L-thyronine with affinities equal to each other (Kd approximately equal to 0.4 nM) and comparable to the nuclear thyroid hormone receptor extracted from rat liver. The relative affinities of a series of thyroid hormone analogs for both translational products were also identical. In various tissues and cell lines, the relative levels of rc-erbA-beta RNA, but not rc-erbA-alpha RNA, correlated with measurements of nuclear 3,5,3'-triiodo-L-thyronine binding sites. Based on this correlation, we suggest that rc-erbA-beta may encode the "classical" nuclear thyroid hormone receptor, whereas rc-erbA-alpha may encode an isoreceptor species with differing functional properties.
Murray
M B
MB
Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455.
Zilz
N D
ND
McCreary
N L
NL
MacDonald
M J
MJ
Towle
H C
HC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000235:genetics / Q000302:isolation & purification*; D004262:DNA Restriction Enzymes; D008099:Liver / Q000032:analysis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012313:RNA / Q000235:genetics; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism
D003062:Codon; D011518:Proto-Oncogene Proteins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D012313:RNA; D004247:DNA; D004262:DNA Restriction Enzymes