Regulation of G protein-coupled receptor kinase subtypes by calcium sensor proteins

被引:72
作者
Sallese, M [1 ]
Iacovelli, L [1 ]
Cumashi, A [1 ]
Capobianco, L [1 ]
Cuomo, L [1 ]
De Blasi, A [1 ]
机构
[1] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Mol Pharmacol & Pathol, I-66030 Santa Maria Imbaro, Italy
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2000年 / 1498卷 / 2-3期
关键词
G protein coupled receptor; G protein coupled receptor kinase; calcium sensor protein; calmodulin;
D O I
10.1016/S0167-4889(00)00088-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
G protein-coupled receptor homologous desensitization is intrinsically related to the function of a class of S/T kinases named G protein-coupled receptor kinases (GRK). The GRK family is composed of six cloned members, named GRK1 to 6. Studies from different laboratories have demonstrated that different calcium sensor proteins (CSP) can selectively regulate the activity of GRK subtypes. In the presence of calcium, rhodopsin kinase (GRK1) is inhibited by the photoreceptor-specific CSP recoverin through direct binding. Several other recoverin homologues (including NCS 1, VILIP 1 and hippocalcin) are also able to inhibit GRK1. The ubiquitous calcium-binding protein calmodulin (CaM) can inhibit GRK5 with a high affinity (IC50 = 40-50 nM). A direct interaction between GRK5 and Ca2+/CaM was documented and this binding does not influence the catalytic activity of the kinase, but rather reduced GRK5 binding to the membrane. These studies suggest that CSP act as functional analogues in mediating the regulation of different GRK subtypes by Ca2+. This mechanism is, however, highly selective with respect to the GRK subtypes: while GRK1, but not GRK2 and GRK5, is regulated by recoverin and other NCS, GRK4, 5 and 6, that belong to the GRK4 subfamily, are potently inhibited by CaM, which had little or no effect on members of other GRK subfamilies. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:112 / 121
页数:10
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