Functional redundancy of the human CCL4 and CCL4L1 chemokine genes.
CCL4 and CCL4L1 are two CC chemokine genes located at chromosome 17q21 whose mature proteins differ at only a single amino acid. Abundant functional information exists for CCL4, however, CCL4L1 has only recently been recognized as a distinct gene, thus information describing it is wanting. The CCL4L1 protein was synthesized in Escherichia coli and compared with the CCL4 protein. Competitive binding studies using HEK-293/CCR5 cells produced comparable EC50 values for the two proteins. Similarly, chemotaxis assays with cells expressing CCR1, CCR3, or CCR5 revealed no substantial differences. CCL4L1 was somewhat more effective at inhibiting HIV-1 replication in PBMCs than was CCL4, however the difference was not statistically significant. These data combined with the observation of individual variation in CCL4L1 gene copy number [Eur. J. Immunol. 32 (2002) 3016, Genomics 83 (2004) 735] support the contention that the CCL4 and CCL4L1 proteins have redundant functions.
Howard
O M Zack
OM
Laboratory of Molecular Immunoregulation, NCI-Frederick, Frederick, MD 21702, USA.
Turpin
Jim A
JA
Goldman
Robert
R
Modi
William S
WS
D000595:Amino Acid Sequence; D002460:Cell Line; D054407:Chemokine CCL4; D018925:Chemokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D019742:Chemokines, CC / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D002633:Chemotaxis / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007928:Lethal Dose 50; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
C066507:CCL4 protein, human; C492768:CCL4L1 protein, human; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D011506:Proteins; D019713:Receptors, CCR5