Regulation of G protein-coupled receptor kinase subtypes by calcium sensorproteins

G protein-coupled receptor homologous desensitization is intrinsically rela ted to the function of a class of S/T kinases named G protein-coupled recep tor kinases (GRK). The GRK family is composed of six cloned members, named GRK1 to 6. Studies from different laboratories have demonstrated that diffe rent calcium sensor proteins (CSP) can selectively regulate the activity of GRK subtypes. In the presence of calcium, rhodopsin kinase (GRK1) is inhib ited by the photoreceptor-specific CSP recoverin through direct binding. Se veral other recoverin homologues (including NCS 1, VILIP 1 and hippocalcin) are also able to inhibit GRK1. The ubiquitous calcium-binding protein calm odulin (CaM) can inhibit GRK5 with a high affinity (IC50 = 40-50 nM). A dir ect interaction between GRK5 and Ca2+/CaM was documented and this binding d oes not influence the catalytic activity of the kinase, but rather reduced GRK5 binding to the membrane. These studies suggest that CSP act as functio nal analogues in mediating the regulation of different GRK subtypes by Ca2. This mechanism is, however, highly selective with respect to the GRK subt ypes: while GRK1, but not GRK2 and GRK5, is regulated by recoverin and othe r NCS, GRK4, 5 and 6, that belong to the GRK4 subfamily, are potently inhib ited by CaM, which had little or no effect on members of other GRK subfamil ies. (C) 2000 Elsevier Science B.V. All rights reserved.