Cloning and characterization of the human granulocyte chemotactic protein-2 gene.
We recently described a novel murine CXC chemokine, designated lipopolysaccharide-induced CXC chemokine (LIX). In an ongoing search for new human chemokines related to LIX, we cloned the gene for human granulocyte chemotactic protein-2 (GCP-2) as well as previously described CXC chemokine genes, including epithelial cell-derived neutrophil-activating peptide-78 (ENA-78). Both coding and noncoding portions of the GCP-2 gene have very high nucleotide similarity to ENA-78, except for the occurrence of a long interspersed DNA-1 sequence 5' of the GCP-2 gene. The GCP-2 gene encodes a propeptide of 114 amino acid residues. The predicted 77-residue mature peptide is identical with the GCP-2 protein previously isolated from MG-63 osteosarcoma cells, except for two additional residues at the carboxyl terminus. We confirmed expression of the gene by Northern analysis and by cloning a portion of the cDNA from reverse transcribed MG-63 cell RNA. Despite 85% identity of the first 270 nucleotides 5' of the transcription start sites, GCP-2 and ENA-78 show cell-specific differences in regulation. GCP-2 is induced in MG-63, but not A549 cells by TNF-alpha, IL-1beta, and LPS, while ENA-78 is expressed in both cell types. Analysis of nucleotide sequence relationships does not support the proposal, by others, that LIX is murine GCP-2. LIX is no more closely related to human GCP-2 than to human ENA-78 and is more distant from both human genes than is porcine alveolar macrophage chemotactic factor-II.
Rovai
L E
LE
Department of Pediatrics, University of California School of Medicine, Los Angeles 90095, USA.
Herschman
H R
HR
Smith
J B
JB
D000595:Amino Acid Sequence; D001483:Base Sequence; D054427:Chemokine CXCL6; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC; D003001:Cloning, Molecular; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017421:Sequence Analysis
C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D018925:Chemokines; D019743:Chemokines, CXC