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-bindi ng 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 huma n 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 stru ctural features that distinguish this family from other GTPases, First, mGB P-2 contains only two of the three consensus sequences for nucleotide bindi ng 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 isopren oid modification, called a CaaX sequence. mGBP-2 is prenylated, as detected by [H-3]mevalonate incorporation, when expressed in COS cells and preferen tially incorporates the C-20 isoprenoid geranylgeraniol, Surprisingly, desp ite having a functional CaaX sequence, mGBP-2 is primarily cytosolic, GBP p roteins are very abundant in IFN-exposed cells, but little is known about t heir 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 possi ble the study of GBP function in the absence of a second family member.