The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide |
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Authors: | Koller Daniela Born Walter Leuthäuser Kerstin Flühmann Beat McKinney R Anne Fischer Jan A Muff Roman |
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Institution: | Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstrasse 340, 8008, Zurich, Switzerland. |
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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. |
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Keywords: | Adrenomedullin Calcitonin gene-related peptide Calcitonin-like receptor Receptor-activity-modifying protein |
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