Chemokine receptors seven-transmembrane

Chemokines are small chemotactic cytokines that act as important messenger molecules between cells of the immune system. Chemokines produce their effects by activating a family of G-protein-coupled receptors. Chemokine receptors are all seven-transmembrane glycoproteins that are structurally related. They may be characterized into those that bind to specific ligands, or those that bind several chemokine ligands. There are also virally encoded (viral) chemokine receptors that represent shared receptors that have been transduced into the viral genome during evolutionary history (Premack and SchaU 1996). 

Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272 872-877 Fernandez EJ, LoUs E (2002) Structure, function, and inhibition of chemokines. Annu Rev Pharmacol Toxicol 42 469-499... 

Chemokines are a superfamily of low-molecular-weight chemotactic cytokines that exert their effects through seven transmembrane domain G protein-coupled receptors. Although some chemokines are constitutively expressed in certain settings, most are induced by proinflammatory mediators, such as IFN-y and TNF-a. Upon binding to the appropriate receptor, chemokines initiate a... 

The seven transmembrane spanning receptor superfamily — Receptors for various chemokines, including IL-8 and MIP... 

Chemokine receptors are a family of G protein-coupled receptors that contain seven transmembrane domains. Chemokine receptors are present on the cell surface membrane of leukocytes. As was the case for chemokines, these receptors are also divided into four subgroups CCR is specific for CC chemokines, CXCR for CXC chemokines, XCR1 for C chemokines and CX3CR1 for CX3C chemokines. The CC chemokine receptor family has eleven members, the CXC chemokine receptor family has seven members, and both the C chemokine receptor family and the CX3C chemokine receptor family have one member each. The signal transduction is mediated via the standard G protein-dependent pathway. 

Cellular Activation. Chemokines are potent cell activators after binding to the appropriate G protein-linked, seven-transmembrane spanning receptors, chemokines elicit transient intracellular calcium flux, actin polymerization, oxidative burst with release of superoxide free radicals, exocytosis of secondary granule constituents, and increased avidity of integrins for their adhesion molecules (Dl, E2). 

Chemokines exert their action through seven-transmembrane receptors, which are GPCRs (Fig. 4.2). Six CXC receptors, 10 CC receptors, and one receptor each for lymphotactin and fractalkine have been identified. Table 4.1 summarizes the human chemokine receptor family, their ligand specificity, and the cell types that predominantly express these receptors. The new nomenclature for chemokines is also included in the table (8). 

The intracellular signals involved in chemo-taxis are not yet fully understood, and much of the information available today has been deduced from signaling information for other GPCRs. However, significant new data regarding the chemotactic process have accumulated in recent years. Like other seven-transmembrane receptors, chemokine receptors couple to G-proteins. Many chemokine-in-duced signaling events are inhibited by Borde-tella pertussis toxin (PTX), suggesting that chemokine receptors are linked to G-proteins of the Gai class (18,19). In cotransfection experiments it has been shown that CXCRl and... 

Receptor dimerization upon ligand binding has been described mostly for the growth factor receptor however, recent reports have also suggested heterodimerization for seven-transmembrane receptors, including chemokine receptors (31 -33). It has been proposedthat che-... 

Figure 4.4. Sequence alignment of human CC and CXC chemokine receptors. For clarity, only the predicted seven (I-VII) transmembrane helical domains are shown.

As mentioned earlier, the biological activities of chemokines are mediated by distinct members of the rhodopsin-like seven-transmembrane domain, G-protein-coupled receptor superfamily [65], Other receptors exist that bind chemokines with high affinity and specificity [16]. However, these receptors are structurally incapable of transducing signals and are therefore designated as decoy receptors. 

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