Cysteine-699, a possible palmitoylation site of the thyrotropin receptor, is not crucial for cAMP or phosphoinositide signaling but is necessary for full surface expression

We investigated the role of the cysteine residues in the cytoplasmic tail of the thyrotropin receptor (TSHR) in TSH binding and signal transduction by individually mutating two cysteine residues to serine. Neither mutant exhibited changes in basal, TSH- or Graves' IgG-stimulated cAMP or inositol phosphate responses. However, mutation of Cys-699 significantly decreased TSH binding B-max without significantly changing binding affinity, amount or sizes of TSHR forms on Western blots. These findings suggest that Cys-699, which is a potential site for lipid modification and whose equivalent in other receptors was shown to bit palmitoylated, is important for efficiency of proper membrane insertion and/or stability of the receptor. (C) 1996 Academic Press, Inc.