Different subcellular localizations for the related interferon-induced GTPases, MuGBP-1 and MuGBP-2: implications for different functions?
The guanylate-binding proteins (GBPs) are a family of 65-67-kDa proteins induced by both type I and type II interferons (IFN). Members of the GBP family of GTPases are among the most abundant IFN-gamma-induced proteins. GBPs contain an unusual GTP binding site, which is consistent with GBP hydrolysis of GTP to both GDP and GMP. In addition, six of the eight known GBPs have a carboxy-terminal CaaX motif for the addition of isoprenyl lipids. Despite their abundance, however, little is known about the biologic function or cellular location of GBPs. We report here on studies to localize both a newly identified murine GBP (MuGBP-2) and its closely related family member, MuGBP-1. In both IFN-treated macrophages and fibroblasts, MuGBP-2 is found in both a granular distribution throughout the cytoplasm and localized to vesicle populations of heterogeneous sizes. The localization of MuGBP-2 to vesicles is dependent on its isoprenylation. Despite a high degree of sequence identity and the presence of an identical CaaX sequence, MuGBP-1 has a very homogeneous cytoplasmic distribution and fails to localize to intracellular vesicles. The different intracellular distribution of these two closely related family members suggests differential function(s).
Vestal
D J
DJ
Department of Molecular Biology of the Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. vestald@ccf.org
Gorbacheva
V Y
VY
Sen
G C
GC
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009154:Mutation; D017368:Protein Prenylation; D014162:Transfection
D004268:DNA-Binding Proteins; C490288:Gbp2b protein, mouse; D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins