Murine GBP-2: a new IFN-gamma-induced member of the GBP family of GTPases isolated from macrophages.
We have cloned a new member of the interferon (IFN)-induced guanylate-binding protein (GBP) family of GTPases, murine GBP-2 (mGBP-2), from bone marrow-derived macrophages. mGBP-2 is located on murine chromosome 3, where it is linked to mGBP-1. With the identification of mGBP-2 there are now two human and two murine GBPs. Like other GBPs, mGBP-2 RNA and protein are induced by IFN-gamma. In addition, mGBP-2 shares with the other GBPs important structural features that distinguish this family from other GTPases. First, mGBP-2 contains only two of the three consensus sequences for nucleotide binding found within the classic GTP binding regions of other GTPases. A second amino acid motif found in mGBP-2 is a potential C-terminal site for isoprenoid modification, called a CaaX sequence. mGBP-2 is prenylated, as detected by [3H]mevalonate incorporation, when expressed in COS cells and preferentially incorporates the C-20 isoprenoid geranylgeraniol. Surprisingly, despite having a functional CaaX sequence, mGBP-2 is primarily cytosolic. GBP proteins are very abundant in IFN-exposed cells, but little is known about their function. mGBP-2 is expressed by IFN-gamma-treated cells from C57Bl/6 mice, whereas mGBP-1 is not. Thus, the identification of mGBP-2 makes possible the study of GBP function in the absence of a second family member.
Vestal
D J
DJ
The Burnham Institute, La Jolla, CA 92037, USA. vestald@cesmtp.ccf.org
Buss
J E
JE
McKercher
S R
SR
Jenkins
N A
NA
Copeland
N G
NG
Kelner
G S
GS
Asundi
V K
VK
Maki
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004790:Enzyme Induction; D020558:GTP Phosphohydrolases / Q000097:blood / Q000302:isolation & purification*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D017368:Protein Prenylation; D017386:Sequence Homology, Amino Acid
D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins