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. 1993 Jul 1;90(13):5994–5998. doi: 10.1073/pnas.90.13.5994

Cloning from the thyroid of a protein related to actin binding protein that is recognized by Graves disease immunoglobulins.

P J Leedman 1, B Faulkner-Jones 1, D S Cram 1, P J Harrison 1, J West 1, E O'Brien 1, R Simpson 1, R L Coppel 1, L C Harrison 1
PMCID: PMC46853  PMID: 8327473

Abstract

Human actin binding protein (ABP) links specific membrane glycoproteins to cytoskeletal actin microfilaments. In human platelets and leukocytes, ABP directly links, respectively, the membrane glycoproteins GPIb and the high-affinity Fc receptor for IgG (Fc gamma IR) to cytoskeletal actin microfilaments. Similar interaction between the thyrotropin (TSH) receptor and ABP in endocrine cells might explain the rapid and profound disruption of actin microfilaments induced by TSH in cultured thyroid follicular cells. By screening a thyroid lambda gt11 cDNA expression library with serum from a Graves disease patient, we identified a clone encoding a protein, designated truncated ABP (TABP), that shares extensive homology (approximately 70%) with ABP. TABP is a truncated ABP-like protein with an open reading frame of 195 aa that encodes a protein of approximately 21 kDa. TABP lacks an actin binding domain but contains two predicted beta-sheet repeats within which is a putative dimerization domain and between which lies a putative glycoprotein binding site containing a consensus site for phosphorylation by Ca(2+)-calmodulin kinase II. TABP contains a unique C-terminal insertion within which lies a hydrophobic predicted membrane-associated region, absent from ABP. Although TABP mRNA is expressed widely, immunoblot analysis demonstrated the presence of TABP antibodies specifically in the sera of a minority of subjects with autoimmune thyroid disease. A 24-residue sequence of similarity was identified between the TSH receptor and platelet glycoprotein GPIb alpha that may represent a transmembrane ABP binding site. We suggest, therefore, that signal transduction by TSH in the thyroid involves direct linkage of the TSH receptor to actin microfilaments by ABP and that TABP may interact with ABP to mediate TSH-induced actin microfilament disruption.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akamizu T., Saji M., Kohn L. D. A microsequencing approach to identify proteins which appear to interact with thyrotropin in rat FRTL-5 thyroid cells. Biochem Biophys Res Commun. 1990 Jul 16;170(1):351–358. doi: 10.1016/0006-291x(90)91281-v. [DOI] [PubMed] [Google Scholar]
  2. Blackshear P. J., Nairn A. C., Kuo J. F. Protein kinases 1988: a current perspective. FASEB J. 1988 Nov;2(14):2957–2969. doi: 10.1096/fasebj.2.14.2972578. [DOI] [PubMed] [Google Scholar]
  3. Fox J. E. Identification of actin-binding protein as the protein linking the membrane skeleton to glycoproteins on platelet plasma membranes. J Biol Chem. 1985 Oct 5;260(22):11970–11977. [PubMed] [Google Scholar]
  4. Gorlin J. B., Yamin R., Egan S., Stewart M., Stossel T. P., Kwiatkowski D. J., Hartwig J. H. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring. J Cell Biol. 1990 Sep;111(3):1089–1105. doi: 10.1083/jcb.111.3.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  7. Kurki P., Miettinen A., Linder E., Pikkarainen P., Vuoristo M., Salaspuro M. P. Different types of smooth muscle antibodies in chronic active hepatitis and primary biliary cirrhosis: their diagnostic and prognostic significance. Gut. 1980 Oct;21(10):878–884. doi: 10.1136/gut.21.10.878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  9. Lawrence T. S., Ginzberg R. D., Gilula N. B., Beers W. H. Hormonally induced cell shape changes in cultured rat ovarian granulosa cells. J Cell Biol. 1979 Jan;80(1):21–36. doi: 10.1083/jcb.80.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leedman P. J., Harrison P. J., Harrison L. C. Immunoblotting for the detection of TSH receptor autoantibodies. J Autoimmun. 1991 Jun;4(3):529–542. doi: 10.1016/0896-8411(91)90164-8. [DOI] [PubMed] [Google Scholar]
  11. Leedman P. J., Newman J. D., Harrison L. C. Human thyrotropin receptor subunits characterized by thyrotropin affinity purification and western blotting. J Clin Endocrinol Metab. 1989 Jul;69(1):134–141. doi: 10.1210/jcem-69-1-134. [DOI] [PubMed] [Google Scholar]
  12. Loosfelt H., Pichon C., Jolivet A., Misrahi M., Caillou B., Jamous M., Vannier B., Milgrom E. Two-subunit structure of the human thyrotropin receptor. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3765–3769. doi: 10.1073/pnas.89.9.3765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McFarland K. C., Sprengel R., Phillips H. S., Köhler M., Rosemblit N., Nikolics K., Segaloff D. L., Seeburg P. H. Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science. 1989 Aug 4;245(4917):494–499. doi: 10.1126/science.2502842. [DOI] [PubMed] [Google Scholar]
  14. Murakami M., Mori M. Identification of immunogenic regions in human thyrotropin receptor for immunoglobulin G of patients with Graves' disease. Biochem Biophys Res Commun. 1990 Aug 31;171(1):512–518. doi: 10.1016/0006-291x(90)91423-p. [DOI] [PubMed] [Google Scholar]
  15. Nagayama Y., Kaufman K. D., Seto P., Rapoport B. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1184–1190. doi: 10.1016/0006-291x(89)92727-7. [DOI] [PubMed] [Google Scholar]
  16. Ohta Y., Stossel T. P., Hartwig J. H. Ligand-sensitive binding of actin-binding protein to immunoglobulin G Fc receptor I (Fc gamma RI). Cell. 1991 Oct 18;67(2):275–282. doi: 10.1016/0092-8674(91)90179-3. [DOI] [PubMed] [Google Scholar]
  17. Piraphatdist T., Sugawa H., Inoue D., Enomoto T., Mori T., Imura H. Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site. Biochem Biophys Res Commun. 1990 Oct 30;172(2):529–536. doi: 10.1016/0006-291x(90)90705-r. [DOI] [PubMed] [Google Scholar]
  18. Rousset B., Bernier-Valentin F., Poncet C., Orgiazzi J., Madec A. M., Monier J. C., Mornex R. Anti-tubulin antibodies in autoimmune thyroid disorders. Clin Exp Immunol. 1983 May;52(2):325–332. [PMC free article] [PubMed] [Google Scholar]
  19. Roustan C., Boyer M., Fattoum A., Jeanneau R., Benyamin Y., Roger M., Pradel L. A. Isolation and structural properties of a high-molecular-weight actin-binding protein (filamin-like protein) in hog thyroid gland. Eur J Biochem. 1982 Dec;129(1):149–155. doi: 10.1111/j.1432-1033.1982.tb07033.x. [DOI] [PubMed] [Google Scholar]
  20. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  21. Tramontano D., Avivi A., Ambesi-Impiombato F. S., Barak L., Geiger B., Schlessinger J. Thyrotropin induces changes in the morphology and the organization of microfilament structures in cultured thyroid cells. Exp Cell Res. 1982 Feb;137(2):269–275. doi: 10.1016/0014-4827(82)90027-1. [DOI] [PubMed] [Google Scholar]
  22. Wadsworth H. L., Chazenbalk G. D., Nagayama Y., Russo D., Rapoport B. An insertion in the human thyrotropin receptor critical for high affinity hormone binding. Science. 1990 Sep 21;249(4975):1423–1425. doi: 10.1126/science.2169649. [DOI] [PubMed] [Google Scholar]
  23. Westermark B., Portor K. R. Hormonally induced changes in the cytoskeleton of human thyroid cells in culture. J Cell Biol. 1982 Jul;94(1):42–50. doi: 10.1083/jcb.94.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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