Activated thyroglobulin possesses a transforming growth factor-beta activity.
Thyroglobulin (Tg), the thyroid hormone precursor, is a major protein component in the thyroid gland and may have other important functions. Here, we show that bovine Tg inhibited 125I-labeled transforming growth factor-beta1 (125I-TGF-beta1) binding to cell-surface TGF-beta receptors in mink lung epithelial cells with an IC50 of approximately 300 nM. After disuccinimidyl suberate (DSS) modification, reduction/alkylation, treatment with 8 M urea, 0. 1% SDS, or acidic pH (pH 4-5), Tg exhibited a approximately 5-10-fold increase of 125I-TGF-beta1 binding inhibitory activity with IC50 of approximately 30-60 nM. This inhibitory activity was an intrinsic property of the Tg and could not be segregated from Tg protein by 5% SDS-polyacrylamide gel electrophoresis or by immunoprecipitation using antiserum to Tg. Untreated Tg did not affect DNA synthesis but blocked the TGF-beta-induced inhibition of DNA synthesis in mink lung epithelial cells. After DSS activation, Tg possessed TGF-beta agonist activity and inhibited DNA synthesis of mink lung epithelial cells and rat thyroid cells. The activated Tg also exerted a small but significant TGF-beta agonist activity in transcriptional activation of plasminogen activator inhibitor-1. These results suggest that Tg possesses an authentic TGF-beta activity which can be induced by chemical modifications and treatments with denaturing agents and acidic pH.
Huang
S S
SS
Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Cerullo
M A
MA
Huang
F W
FW
Huang
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D008907:Mink; D008969:Molecular Sequence Data; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011489:Protein Denaturation; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013388:Succinimides / Q000378:metabolism; D013954:Thyroglobulin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014508:Urea / Q000494:pharmacology
D019384:Nucleic Acid Synthesis Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides; D016212:Transforming Growth Factor beta; C028721:disuccinimidyl succinate; D012967:Sodium Dodecyl Sulfate; D014508:Urea; D013954:Thyroglobulin