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

Peter J. Leedman, Beverley Faulkner-Jones, David S. Cram, Paul J. Harrison, Jeanette West, Elizabeth O'Brien, Richard Simpson, Ross L. Coppel, Leonard C. Harrison

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 (FcγIR) 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 λgt11 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 (≈70%) with ABP. TABP is a truncated ABP-like protein with an open reading frame of 195 aa that encodes a protein of ≈21 kDa. TABP lacks an actin binding domain but contains two predicted β-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 Ca2+-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 GPIbα 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.

Original languageEnglish
Pages (from-to)5994-5998
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number13
DOIs
Publication statusPublished - 1 Jul 1993
Externally publishedYes

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