An N-linked glycosylation motif from the noncleaving luteinizing hormone receptor substituted for the homologous region (Gly(367) to Glu(369)) of the thyrotropin receptor prevents cleavage at its second, downstream site

作者：Kakinuma A; Chazenbalk GD; Tanaka K; Nagayama Y; McLachlan SM; Rapport B

来源：Journal of Biological Chemistry, 1997, 272(45): 28296-28300.

DOI：10.1074/jbc.272.45.28296

The thyrotropin receptor (TSHR) exists in two forms (single polypeptide and two subunits), whereas the lutropin/chorionic gonadotropin receptor (LH/CGR) is a single chain, Recent data suggest that the TSHR cleaves at two sites, We mutagenized selected chimeric TSH-LH/CGR to localize the cleavage sites in the TSHR, All 23 receptors mutated in the estimated vicinity of the upstream site cleaved into two subunits as determined by I-125-TSH cross-linking to intact cells, In contrast, in a series of mutations homologous to the noncleaving LH/GGR, the downstream TSHR cleavage site localized to three amino acids (GQE(367-369)). Remarkably, group substitution of these residues, but not substitution of individual residues, abolished cleavage, Moreover, the mutation that prevented cleavage (GQE(367-369)NET) transposed a motif (NET291-293) that is glycosylated in the LH/CGR, TSHR cleavage or noncleavage after substitution of GQE(367-369) with Other triplets (AAA, NQE, and NQT) was consistent with a role for N-linked glycosylation at this site.
In summary, our data (i) support the concept that the TSHR cleaves at two sites, (ii) relate TSHR residues GQE(367-369) to cleavage at the second, downstream site, and (iii) suggest that cleavage or noncleavage at site two is related to N-linked glycosylation. These findings provide new insight into the evolutionary divergence of two closely related receptors.

• 出版日期1997-11-7