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CLONING FROM THE THYROID OF A PROTEIN RELATED TO ACTIN-BINDING PROTEIN THAT IS RECOGNIZED BY GRAVES-DISEASE IMMUNOGLOBULINS


LEEDMAN, PJ; FAULKNERJONES, B; Cram, DS; Harrison, PJ; WEST, J; OBRIEN, E; Simpson, R; Coppel, RL; Harrison, LC
1993-07-01
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal Article
90
13
5994-5998
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 (FcgammaIR) 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 lambdagt11 cDNA expression library with serum from a Graves disease patient, we identified a done encoding a protein, designated truncated ABP (TABP), that shares extensive homology (almost-equal-to 70%) with ABP. TABP is a truncated ABP-like protein with an open reading frame of 195 aa that encodes a protein of almost-equal-to 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 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 GPIbalpha 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.
NATL ACAD SCIENCES
HUMAN THYROTROPIN RECEPTOR; TSH RECEPTOR; CELLS; IDENTIFICATION; PURIFICATION; ANTIBODIES; SEQUENCE; FILAMIN
10.1073/pnas.90.13.5994
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Creation Date 1993-07-01 12:00:00