Chemokine receptors promiscuous binding

Chemokines exhibit complex ligand-receptor relationships. Often, individual chemokines can bind productively to more than one receptor, and many chemokine receptors can signal in response to more than one chemokine. Usually, these chemokine receptors bind multiple chemokines within the same subfamily. The best documented example of chemokine receptor promiscuity across subfamilies involves CXCR3 binding to CCL21. 

TM) GPCRs, and the identification of these two molecules facilitated the discovery of many of the other chemokine receptors. The identification of the two IL8 receptors was followed, shortly after, by the cloning of a receptor for CC chemokines. This receptor was initially called CC-CKR1 (now CCR1) and was shown to promiscuously bind a number of members of the CC chemokine family (6). Subsequent to the identification of these three chemokine receptors, two principal methods have been used to clone the cDNAs for the other currently identified receptors ... 

Interestingly, there is a certain degree of promiscuity in the chemokine superfamily with many ligands binding different receptors or vice versa. So-called cluster chemokines representing chemotactic proteins which share a distinct chromosomal location are likely to bind the same receptors. However, noncluster or microcluster chemokines are ligands which demonstrate a unique chromosomal location and tend to present a restricted or even specific chemokine receptor interaction [23]. 

There are two major classes of chemokine receptors. The CC receptors bind to the CC chemokines and are named CCRl to 9 the CXC chemokines selectively bind to the CXC receptors, termed CXCRl to CXCR5. This group also comprises receptors for fractalkine (CX3CRI) and lymphotactin (XCRl), as well as the Duffy antigen receptor for chemokines (DARC), which has been shown to bind promiscuously to both CXC and CC chemokines. Finally, there is a receptor termed D6, which has been renamed CCRIO by some investigators. 

Chemokines bind to seven transmembrane domain proteins coupled to GTP-binding proteins with homology to the family of chemotactic receptors. Five receptors for C-X-C chemokines (CXCRl to 5) and nine for C-C chemokines (CCRl to 9) were recently cloned (Table 1). These receptors show a promiscuous pattern of ligand recognition and are differentially expressed and regulated in leukocytes (Baggiolini et al., 1997 Izumi et al., 1997 Nibbs et al., 1997 Rollins, 1997 Legler et al., 1998). The... 

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