Thyrotropin (TSH) receptor residue E251 in the extracellular leucine-rich repeat domain is critical for linking TSH binding to receptor activation.

ABSTRACT: The TSH receptor (TSHR) ectodomain comprises a tubular leucine-rich repeat domain (LRD) and a hinge [or signaling specificity domain (SSD)]. TSH binds to both the LRD and SSD, leading to signal transduction by the transmembrane domain. The SSD structure and spatial orientation to the other components are unknown. We exploited a fortuitous observation to obtain mechanistic insight into the relationship between TSH binding and signal transduction. A mouse TSHR cDNA generated by PCR was found to express a receptor with poor TSH-induced cAMP generation despite normal TSH binding. Progressive reversion to wild-type of six mutations revealed E251K in the LRD to be critical for reduced signal transduction in both mouse and human TSHR. An I286F substitution in the SSD had a much weaker effect and

SUBMITTER: Chen CR 

PROVIDER: S-EPMC2851189 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature