Murine GBP-5, a new member of the murine guanylate-binding protein family, is coordinately regulated with other GBPs in vivo and in vitro.
A new murine member of the interferon (IFN)-inducible guanylate-binding protein (GBP) family was cloned in a search for glucocorticoid-attenuated response genes induced in the lung during endotoxemia. The full-length MuGBP-5 cDNA encodes a 590 amino acid residue protein with GTP binding motifs identical to those in human GBP-1 (HuGBP-1) and a similar isoprenylation sequence at the C-terminus. An alternatively spliced form of MuGBP-5 that lacks the second GTP binding motif and differs at the C-terminus was also identified. The MuGBP-5 gene is located on chromosome 3, near MuGBP-3 and MuGBP-2, and has a genomic organization similar to other GBP genes. To facilitate the evaluation of GBP family message expression, we constructed RNase protection assay probes for MuGBP-1, MuGBP-2, MuGBP-3, MuGBP-4/Mag-2 (macrophage activation gene-2), and MuGBP-5 and validated their use in Swiss Webster, BALB/c, and C57BL/6 mice. In BALB/c mice, all five MuGBPs were induced in multiple organs during endotoxemia, and all had a similar pattern of expression in different tissues. With minor quantitative differences, the MuGBPs also had similar patterns of response to IFN-gamma, lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in RAW 264.7 and Swiss 3T3 cells. The coordinate expression of the MuGBPs suggests that they share common mechanisms of regulation.
Nguyen
Tam Thuan
TT
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Hu
Yan
Y
Widney
Daniel P
DP
Mar
Rebecca A
RA
Smith
Jeffrey B
JB
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000315:Adrenalectomy; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D019446:Endotoxemia / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D010802:Phylogeny; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C490287:GBP1 protein, human; C113264:GBP3 protein, human; C490288:Gbp2b protein, mouse; C485134:Gbp3 protein, mouse; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C452200:Gbp2 protein, mouse; C472531:Gbp5 protein, mouse; C472530:Mpa2 protein, mouse