Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma.
Interferon gamma is a pleiotropic cytokine that regulates many immune functions. We have identified a novel protein, inducibly expressed GTPase (IGTP), whose expression was regulated by interferon gamma in macrophages. In mouse RAW 264.7 macrophages, IGTP mRNA levels were almost undetectable but increased within 1 h of exposure to interferon gamma, peaked at very high levels within 3 h, and remained at high levels to at least 48 h; pretreatment of the cells with cycloheximide blocked the majority of mRNA accumulation. In the mouse, the mRNA was highly expressed in thymus, spleen, lung, and small intestine. Using interspecific backcross analysis, the Igtp gene was mapped to mouse chromosome 11. The IGTP cDNA encoded a putative polypeptide of Mr 48,507 and pI 7.79 that contained three consensus GTP binding motifs, GXXXXGK(S/T), DXXG, and NTKXD. Both IGTP that had been immunoprecipitated from RAW cells and a glutathione S-transferase IGTP fusion protein were able to convert GTP to GDP in vitro. Subcellular protein fractionation and Western blotting localized IGTP to the cytosol of RAW cells. In addition, the protein was homologous to proteins encoded by three previously cloned cDNAs, IRG-47, TGTP/Mg21, and LRG-47, and thus may be representative of a new family of interferon gamma-regulated GTPases.
Taylor
G A
GA
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Jeffers
M
M
Largaespada
D A
DA
Jenkins
N A
NA
Copeland
N G
NG
Vande Woude
G F
GF
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction; D005347:Fibroblasts / Q000201:enzymology; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D007371:Interferon-gamma / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D000076106:SAM Domain and HD Domain-Containing Protein 1; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D007371:Interferon-gamma; D003513:Cycloheximide; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020558:GTP Phosphohydrolases; C101131:Igtp protein, mouse; D020559:Monomeric GTP-Binding Proteins