The shed thyrotropin receptor is primarily a carboxyl terminal truncated form of the A subunit, not the entire A subunit.
The TSH receptor (TSHR) sheds its A subunit, particularly when cells are cultured in serum-poor medium. This shed A subunit is reported to be smaller than the cell-associated receptor because of the loss of glycan without change in its polypeptide core. Contrary to previous deductions, we now find that the 'small' shed A subunit has lost a glycan moiety because of the proteolytic clipping of a small C-terminal fragment containing an Asn-linked glycan. Moreover, this lost peptide fragment contains cysteine residues likely involved in A subunit linkage to the membrane-associated B subunit. Progressive lowering of the serum concentration in culture medium accentuates the process. Therefore, 'small' A subunit shedding does not appear related to a physiological mechanism involving disulfide bond reduction. On the other hand, we detected, for the first time, shedding of a lesser amount of normal-sized, in addition to small, A subunits, especially by cells cultured in standard serum concentrations.
Cedars-Sinai Research Institute and the School of Medicine, University of California, Los Angeles, USA.
K
K
Tanaka
G D
GD
Chazenbalk
S M
SM
McLachlan
B
B
Rapoport
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016895:Culture Media, Serum-Free; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011989:Receptors, Thyrotropin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D016895:Culture Media, Serum-Free; D011989:Receptors, Thyrotropin