1992 Fiscal Year Final Research Report Summary
Metabolism and regulation mechanism of a 55k-Da multifunctional protein.
| Project/Area Number |
03671042
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | GUNMA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
HORIUCHI Ryuya Gunma University School of Medicine, Department of Pharmacy, Professor, 医学部附属病院, 教授 (90008342)
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| Project Period (FY) |
1991 – 1992
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| Keywords | multifunctional protein / Protein Disulfide Isomerase / Thyroid Hormone / Binding Sites / Regulation Mechanism / T_3 binding protein |
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| Research Abstract |
We showed recently that a membrasne-associated 3,5,3'-L-triiodothyronine (T_3) binding protein of 55 kDa (55k-MFP), a multifunctional protein, was identical with protein disulfide isomerase (PDI), which catalizes the formation and rearrangement of disulfide bonds in various proteins. In the present study, we showed that the recombinant 55k-MFP (r55k-MFP) and placenta 55k-MFP (p55k-MFP) purified from recombinant Escherichia coli transformed with human 55k-MFP cDNA expression plasmid and from normal human placenta, respectively have similar T_3-binding activity and PDI activity determined by refolding of scrambled pancreatic RNase. Furthermore, the PDI activity of both proteins was dose-dependently inhibited by T_3 in vitro. The inhibitory effect of iodothyronines was stereospecific (T_3=D-T_3>>L-thyroxine). A significant inhibition was induced by T_3 at the same molar concentration with the purified proteins, and the ED_<50>s of T_3 were about 15 times higher than that the concentrations of the proteins. The T_3 binding site in the molecule was identified to be the active site region expressing PDI activity by the sequence analysis of the peptide labeled with Bromoacetyl [^<125>I]T_3. These results suggest that the binding of T_3 to 55k-MFP in the target cells might regulate the formation or reconstruction of protein disulfide bonds, probably having a significant effect on thyroid hormone actions on target cells.
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[Publications] Iino, Y., Yoshida, M., Tago, T., Owada, S., Sugamata, N. and Horiuchi, R.: "Effects of sequential and combined immuno-endocrine therapies using OK-432 (Picibanil) and Tamoxifen on the growth of 7,12-Dimethylbenz[a]anthracene-induced rat mammary carcinoma." Jpn. J. Clin. Oncol.21. 35-38 (1991)
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[Publications] Iino, Y., Sugamata, N. Owada, S., Tago, T., Sato, H., Yokoe, T., Maemura, Y., Morishita, Y. and Horiuchi, R.,: "Antitumor effects of a nonsteroidal aromatase inhibitor (CGS 16949A0 on 7,12-Dimethylbenz[a]anthracene-induced mammary tumors in rats." Jpn. J. Clin. Oncol.21. 153-159 (1991)
Description
「研究成果報告書概要(欧文)」より
