Thyrotropin receptor cleavage at site 1 does not involve a specific amino acid motif but instead depends on the presence of the unique, 50 amino acid insertion.

The Journal of Biological Chemistry
K TanakaBasil Rapoport

Abstract

Thyrotropin (TSH) receptor (TSHR) A and B subunits are formed by intramolecular cleavage of the single chain receptor at two separate sites. The region involved in cleavage at Site 2 has been identified, but previous mutagenesis studies failed to identify Site 1. We now report fortuitous observations on the effect of trypsin on the TSHR that localizes a small region harboring Site 1. Thus, as detected by immunoblotting and by 125I-TSH cross-linking to TSHR expressed on the surface of intact CHO cells, trypsin clipped a small polypeptide fragment bearing a glycan moiety from the C terminus of the A subunit. Based on the TSHR primary structure, this small fragment (1-2 kDa) contains Asn-302. This information, together with estimation of the size of the deglycosylated A subunit relative to a series of C-terminal truncated TSHR ectodomain variants, places cleavage Site 1 in the vicinity of, or closely upstream to, residue 317. Remarkably, mutagenesis of every amino acid residue between residues 298-316 (present study) and 317-362 (previous data) did not prevent cleavage at Site 1. However, cleavage at this site was abrogated by deletion of a 50-amino acid segment (residues 317-366) unique to the TSHR in the glycoprotein hormone rec...Continue Reading

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Citations

Aug 16, 2003·European Journal of Biochemistry·Mylène QuellariMicheline Misrahi
Apr 6, 2001·Thyroid : Official Journal of the American Thyroid Association·K TanakaS M McLachlan
May 1, 2001·Thyroid : Official Journal of the American Thyroid Association·M MaruyamaB Rees Smith
Aug 24, 2002·Thyroid : Official Journal of the American Thyroid Association·Urszula PiotrowskaJ Paul Banga
Feb 21, 2003·Thyroid : Official Journal of the American Thyroid Association·Jennifer JeffreysBernard Rees Smith
Feb 24, 2001·Thyroid : Official Journal of the American Thyroid Association·Y OdaB R Smith
Sep 8, 2007·Thyroid : Official Journal of the American Thyroid Association·Basil Rapoport, Sandra M McLachlan
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May 26, 2007·Trends in Endocrinology and Metabolism : TEM·Romy Kursawe, Ralf Paschke
Jun 24, 2004·Clinical Endocrinology·Sandra M McLachlan, Basil Rapoport
Nov 23, 2016·Journal of Molecular Endocrinology·Ricardo Núñez MiguelBernard Rees Smith
Jan 29, 2019·Journal of Molecular Endocrinology·Jennifer Miller-GallacherBernard Rees Smith
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