Document Detail


Reassessment of the location of the thyrotropin receptor 50 amino acid "insertion" provides evidence in favor of a second downstream cleavage site.
MedLine Citation:
PMID:  11288979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cleavage of thyrotropin receptors (TSHR) on the cell surface into disulfide-linked A and B subunits involves deletion of an intervening region that corresponds approximately to a 50 amino acid "insertion" in the TSHR relative to the noncleaving luteinizing hormone/choriogonadotropin receptor (LH/CGR). The location of this insertion is imprecise because of the relatively low homology between the two receptors in this region. We tested the hypothesis that the TSHR 50 amino acid insertion was further downstream than we previously concluded, a possibility that would relocate the crucial LH/CGR glycan at N291 relative to the position of the TSHR insertion, and that would mitigate against the 50 amino acid insertion playing a role in TSHR intramolecular cleavage. Thus, we transferred the LH/CGR glycan at amino acid 291 from downstream (N367) to upstream of the 50 amino acid insertion (N317) in the TSHR, leaving this insertion intact. TSHR cleavage persisted. Moreover, deletion of amino acid residues 320-366 in addition to the upstream N291 substitution (ALN317-319NET) also did not prevent cleavage. On the other hand, deletion of three contiguous downstream residues (GQE367-369) in the TSHR 50 amino acid insertion abolished receptor cleavage into subunits. In summary, the present data are consistent with our previous location of the TSHR 50 amino acid insertion and, therefore, do not undermine evidence for the involvement of this insertion in TSHR cleavage. In addition, the data regarding TSHR residues GQE367-369 (far downstream of cleavage site 1) support the controversial possibility of a secondary cleavage site downstream of the insertion.
Authors:
K Tanaka; G D Chazenbalk; B Rapoport; S M McLachlan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Thyroid : official journal of the American Thyroid Association     Volume:  11     ISSN:  1050-7256     ISO Abbreviation:  Thyroid     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-04-05     Completed Date:  2001-07-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9104317     Medline TA:  Thyroid     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-4     Citation Subset:  IM    
Affiliation:
Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California, Los Angeles, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence / genetics
Animals
CHO Cells
Cricetinae
Cross-Linking Reagents / pharmacology
DNA Transposable Elements*
Gene Deletion
Molecular Sequence Data
Mutation / genetics
Receptors, Thyrotropin / genetics*
Grant Support
ID/Acronym/Agency:
DK19289/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cross-Linking Reagents; 0/DNA Transposable Elements; 0/Receptors, Thyrotropin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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