Binding of 3,5,3'-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3.
We have compared the affinities for T3 and the T3 analog binding characteristics of the in vitro translational products of seven c-erbA cDNAs (chicken c-erbA alpha; human placental c-erbA beta; rat c-erbA beta-1; rat c-erbA alpha-1; rat c-erbA alpha-2; human testis c-erbA alpha-2; and human kidney c-erbA alpha-2). Four of these (chicken c-erbA alpha, human placental c-erbA beta, rat c-erbA beta-1, rat c-erbA alpha-1) bound T3 with high affinity as previously described. When compared under identical conditions of synthesis and [125I]T3 binding, there was no significant difference between the affinity of the chicken c-erb A alpha-1 and the human c-erbA beta but in a more limited series the affinity of rat c-erbA beta-1 for T3 was 4.6-fold higher than that of the rat c-erbA alpha-1. In vitro translational products of the beta-probes showed a characteristic 2.2-fold higher triiodothyroacetic acid/T3 ratio than did the products of the alpha-probes, regardless of the species of origin of the probe. As previously established, the rat c-erbA alpha-2 product did not bind T3. However, in contrast to two published reports, the human testis and kidney alpha-2 probe products also failed to bind T3. These findings indicate that highly conserved C-terminal 37-40 residues are important for high affinity T3 binding by proteins encoded by the c-erb A family of genes.
Schueler
P A
PA
Department of Medicine, University of Minnesota, Minneapolis 55455.
Schwartz
H L
HL
Strait
K A
KA
Mariash
C N
CN
Oppenheimer
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015342:DNA Probes; D004591:Electrophoresis, Polyacrylamide Gel; D015698:Genomic Library; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D013737:Testis / Q000378:metabolism; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000378:metabolism*
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D004247:DNA