PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus

Biochem Biophys Res Commun. 2003 Nov 7;311(1):24-31. doi: 10.1016/j.bbrc.2003.09.157.


COOH-terminal cytoplasmic domains of G protein-coupled receptors (GPCRs) have been shown to carry determinants that control their cell surface localization, internalization, and recycling. In attempts to seek cellular proteins that mediate these processes of PTH/PTH-related protein receptor (PTHR), one of the class B GPCRs, we have found that Tctex-1, a 14kDa light chain of cytoplasmic dynein motor complex, interacts with the COOH-terminal tail of the receptor. A 34-amino-acid stretch of the receptor responsible for binding to Tctex-1 has a bipartite structure consisting of a motif previously implicated in binding of some proteins to Tctex-1 and a putative new consensus sequence. Site-directed mutations or a 20-amino-acid deletion in the bipartite consensus binding sequence abolished the association of the PTHR COOH terminus with Tctex-1 in vitro. A GFP-fused mutant PTHR impaired in binding to Tctex-1 expressed in MDCK cells showed a decreased rate of internalization in response to PTH compared to that of the wild type.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Brain / metabolism
  • Brain Chemistry
  • Carbon Dioxide / chemistry
  • Carbon Dioxide / metabolism
  • Consensus Sequence
  • Cytoplasm / chemistry*
  • Cytoplasm / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Kidney / chemistry
  • Kidney / metabolism
  • Microtubule Proteins / chemistry*
  • Microtubule Proteins / metabolism*
  • Microtubule-Associated Proteins*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Peptide Fragments
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptor, Parathyroid Hormone, Type 1 / agonists
  • Receptor, Parathyroid Hormone, Type 1 / chemistry*
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • t-Complex Genome Region


  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • Receptor, Parathyroid Hormone, Type 1
  • Carbon Dioxide
  • carboxyl radical
  • GTP-Binding Proteins