Chemokines families

The HIV-1 coreceptors CXCR4 and CCR5 bind to ligand members of a family of molecules known as chemokines, or chemotactic cytokines. While the hallmark function of these small proteins is the direction of leukocyte trafficking, they can also participate in cellular events such as activation and costimulation (Bajetto et al. 2(X)la). Members of the chemokine family can be classified as either homeostatic or inflammatory based on their temporal expression (Charo and Ransohoff 2006 Kim 2005). Although traditionally the CNS had been thought to be protected from immune acti-... 

Aside from providing the targets for HIV-1-induced neuropathogenesis, researchers have also studied the normal functions served by chemokines in the nervous system. One answer to this question can be obtained by considering the evolution of chemokines and their receptors. There are a large number of chemokines that have been identified to date, more than 50 in most mammals. As far as we know, all the actions of chemokines are transduced through stimulation of a family of related, G protein-coupled receptors (Tran and Miller 2003). Research into the pattern of evolution of chemokines and their receptors has revealed that a large expansion of the chemokine family occurred in parallel with the development of a sophisticated... 

The organization of chemokine families based on the cysteine sequence has functional significance. Some human chemokines can compete for binding and activation of receptors with other intrafamily chemokines. This raised the possibility that significant structural differences in chemokine-receptor interactions... 

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 ... 

Broxmeyer HE, Kim CH. Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities. Exp Hematol 1999 27(7) 1113—1123. 

Lambeir AM, Proost P, Durinx C, et al. Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J Biol Chem 2001 276(32) 29839-29845. 

Based on the structural/functional difference, the members of the CXC chemokine family are unique cytokines in their ability to behave in a disparate manner in the regulation of angiogenesis. The angiogenic members include... 

Baggiolini M, Loetscher P, Moser B. 1995. Interleukin-8 and the chemokine family. Int J Immunopharmacol 17 103-108. 

HIV enters the host cell by fusing the lipid membrane of the virus with the host cell membrane. This fusion is triggered by the interaction of proteins on the surface of the HIV envelope with specific cell surface receptors. One of these is CD4, the main receptor for HIV-1 that binds to gpl20, a surface protein on the virus particle.5 CD4 alone, however, is not sufficient to permit HIV fusion and cell entry-an additional co-receptor from the chemokine family of G-protein coupled receptors (GPCRs) is required. The chemokine receptor CCR5 has been demonstrated to be the major co-receptor for the... 

Fig. 2. The Chemokine Family. Dendogram showing the similarities between the human and virally encoded chemokine protein sequences. The sequences cluster in terms of the level of identity pairs of amino acids. The further to the right that the branch points are shown on the diagram, the more similar the two proteins are.

Only the primary sequence of MDC is known. MDC is a member of the CC family of chemokines and shares 28-35% amino acid identity with this group of proteins. This sequence conservation includes the four characteristic cysteines and nine other highly conserved residues (Chang et al., 1997 Godiska et al, 1997). At the C-terminus of MDC there is a stretch of basic residues which is also conserved within the chemokine family and which mediates their ability to interact with heparin. 

No information is available. The genomic structure of MDC has been determined and the intron-exon boundaries are conserved between MDC and other members of the CC chemokine family. In addition the 3 untranslated region of the MDC cDNA is longer than that of other chemokines and includes three Alu repeats (Godiska et al, 1997). 

Other amphipathic p-sheet forming peptides have been derived from proteins in the a-chemokine family [23] which includes platelet factor-4 (PF4) [24], interleukin-8 (IL-8) [25] and growth related protein (Gro-a) [26]. 

For the chemokine family, six different chemokine receptors have been identified and cloned (Neote etal.,... 

Chemokine family. The mediators are divided into four subclasses according to chemical characteristics of the ligands, namely the number or positions of cyteine residues, as follows CC chemokines CXC chemokines CX3C chemokine C chemokines. These chemokines act at receptors largely named after the peptides themselves, and include CCCRl-8 and CXRl-4. (Chemokines recognized include MIP-la MIP-ip MCP-1 MCP-2 MCP-3 MCP-4 MIP-5 RANTES LCRl leukotactin-1 eotaxin, eotaxin-1 and some other chemokines. 

Currently, from a practical viewpoint, cytokines are classified as belonging to (1) hemopoietin, (2) interferon, (3) tumor necrosis factor (TNF), or (4) chemokine families. 

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