Premium
Rat RAMP domains involved in adrenomedullin binding specificity
Author(s) -
Kuwasako Kenji,
Kitamura Kazuo,
Onitsuka Hisamitsu,
Uemura Tomohiko,
Nagoshi Yasuko,
Kato Johji,
Eto Tanenao
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02721-7
Subject(s) - adrenomedullin , receptor , agonist , hek 293 cells , enzyme linked receptor , microbiology and biotechnology , chemistry , 5 ht5a receptor , interleukin 21 receptor , biology , biochemistry , endocrinology
When coexpressed with receptor activity‐modifying protein (RAMP)2 or ‐3, calcitonin receptor‐like receptor (CRLR) functions as an adrenomedullin (AM) receptor (CRLR/RAMP2 or ‐3). Coexpression of rat (r)CRLR with rRAMP deletion mutants in HEK293T cells revealed that deletion of residues 93–99 from rRAMP2 or residues 58–64 from rRAMP3 significantly inhibits high‐affinity [ 125 I]AM binding and AM‐evoked cAMP production, despite full cell surface expression of the receptor heterodimer. Apparently, these two seven‐residue segments are key determinants of high‐affinity agonist binding to rAM receptors and of receptor functionality. Consequently, their deletion yields peptides that are able to serve as negative regulators of AM receptor function.