Rat RAMP domains involved in adrenomedullin binding specificity

FEBS Letters

Kato, Johji¹  Onitsuka, Hisamitsu¹  Eto, Tanenao¹  Nagoshi, Yasuko¹  Uemura, Tomohiko¹  Kitamura, Kazuo¹  Kuwasako, Kenji¹ 

[1] First Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan

关键词: Adrenomedullin;    Receptor activity-modifying protein;    Calcitonin receptor-like receptor;    AM;    adrenomedullin;    BSA;    bovine serum albumin;    CGRP;    calcitonin gene-related peptide;    CRLR;    calcitonin receptor-like receptor;    FACS;    fluorescence-activated cell sorting;    FITC;    fluorescein isothiocyanate;    PBS;    phosphate-buffered saline;    PCR;    polymerase chain reaction;    RAMP;    receptor activity-modifying protein;   

DOI  :  10.1016/S0014-5793(02)02721-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 [¹²⁵I]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.

【 授权许可】

Unknown