The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide

FEBS Lett. 2002 Nov 20;531(3):464-8. doi: 10.1016/s0014-5793(02)03585-8.

Abstract

The calcitonin (CT)-like (CL) receptor is a CT gene-related peptide (CGRP) receptor or an adrenomedullin (AM) receptor when co-expressed with receptor-activity-modifying proteins (RAMP) 1 or 2, respectively. The CL receptor shows 57% overall sequence identity with the CT receptor, but the homology is much lower in the extreme N-terminus. An N-terminal deletion mutant of the human (h) CL receptor (Delta18-hCL) and a chimeric receptor consisting of the N-terminal amino acids of the porcine (p) CT receptor fused to the Delta18-hCL receptor (pCT-hCL) were therefore analyzed. The Delta18-hCL receptor function was abolished when co-expressed with RAMP1 or -2. The pCT-hCL receptor was a fully functional CGRP receptor when co-expressed with RAMP1, but the RAMP2-dependent AM receptor function was impaired. Limited sequence similarities in the N-terminus of the pCT and the hCL receptors rescue CGRP but not AM receptor binding and signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcitonin Gene-Related Peptide / metabolism*
  • Calcitonin Receptor-Like Protein
  • Cricetinae
  • Humans
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Protein Binding
  • Receptors, Calcitonin / chemistry
  • Receptors, Calcitonin / genetics
  • Receptors, Calcitonin / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • CALCRL protein, human
  • Calcitonin Receptor-Like Protein
  • Peptides
  • Receptors, Calcitonin
  • Adrenomedullin
  • Calcitonin Gene-Related Peptide