受体活性修饰蛋白研究进展

受体活性修饰蛋白(receptor activity-modifying proteins,RAMPs)属于单跨膜蛋白家族,分三个结构域,RAMP的N端和跨膜区决定本身的功能和受体表型,胞内C端对于配体的信号传导和受体循环有重要作用。目前发现有三个成员:RAMP1、RAMP2和RAMP3。RAMPs通过改变G蛋白偶联受体的糖基化,作用于配体结合区域来调节受体表型。RAMP1与降钙素受体样受体(calcitonin receptor like receptor,CRLR)结合表现出降钙素基因相关肽(calcitonin gene-related peptide,CGRP)受体表型:RAMP2和RAMP3与CRLR结合则对肾上腺髓质素(adrenomedullin,AM)表现高亲和力,与降钙素受体(calcitonin receptor,CTR)结合则作为胰淀粉样酶(amylin,AMY)受体。由此可见,RAMPs不仅调节受体与配体结合,还影响细胞内的蛋白相互作用调节细胞内信号传导来影响细胞的增殖、迁移、分化等生物学特性。RAMPs还对心血管系统的病理生理有重要调节作用。

The advancement of receptor activity-modifying proteins

Receptor activity-modifying proteins (RAMPs) belong to single-transmembrane spanning proteins family,and have three function domains.The N-terminal and transmembrane domains play a principal role in the determination of receptor phenotype and the C-tail domain is related to cellular signal transduction.RAMPs have three members:RAMP1,RAMP2 and RAMP3.RAMPs regulate receptor phenotype by transforming the glycosylation of G-protein couple receptor and interacting with ligand binding domain.The calci- tonin gene-related peptide (CGRP) receptor phenotype is determined by RAMP1 interacting with calcitonin receptor like receptor (CRLR),but the CRLR behaves an adrenomedullin (AM) receptor phenotype by binding RAMP2 or RAMP3,respectively;Caicitonin re- ceptor(CTR) also behaves an amylin (AMY) receptor phenotype by interacting with RAMPs.So,RAMPs not only determine the binding of receptor and legnad but also regulate the cellular signal transduction,which affects the biological characteristics of cells,such as prolif- eration,migration and differentiation,etc.RAMPs also play an important role in accommodating pathology and physiology of cardiovas- cular system.