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

FEBS Letters

Born, Walter¹  McKinney, R.Anne²  Koller, Daniela¹  Fischer, Jan A¹  Muff, Roman¹  Flühmann, Beat¹  Leuthäuser, Kerstin¹ 

[1]Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstrasse 340, 8008 Zurich, Switzerland

[2]Brain Research Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland

关键词: Adrenomedullin;    Calcitonin gene-related peptide;    Calcitonin-like receptor;    Receptor-activity-modifying protein;    AM;    adrenomedullin;    CGRP;    calcitonin gene-related peptide;    CL;    calcitonin-like;    CT;    calcitonin;    RAMP;    receptor-activity-modifying protein;   

DOI  :  10.1016/S0014-5793(02)03585-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (Δ18-hCL) and a chimeric receptor consisting of the N-terminal amino acids of the porcine (p) CT receptor fused to the Δ18-hCL receptor (pCT–hCL) were therefore analyzed. The Δ18-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.

【 授权许可】

Unknown