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Prenylation of an interferon‐γ‐induced GTP‐binding protein: the human guanylate binding protein, huGBP1
Author(s) -
Nantais David E.,
Schwemmle Martin,
Stickney John T.,
Vestal Deborah J.,
Buss Janice E.
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.60.3.423
Subject(s) - biology , prenylation , gtp' , gtp binding protein regulators , binding protein , interferon , plasma protein binding , biochemistry , g protein , signal transduction , virology , enzyme , gene
Interferons (IFN) and lipopolysaccharide (LPS) cause multiple changes in isoprenoid‐modified proteins in murine macrophages, the most dramatic being the expression of a prenyl protein of 65 kDa. The guanylate binding proteins (GBPs) are IFN‐inducible GTP‐binding proteins of ~65 kDa that possess a C aa X motif at their C‐terminus, indicating that they might be substrates for prenyltransferases. The human GBP1 protein, when expressed in transfected COS‐1 cells, incorporates radioactivity from the isoprenoid precursor [ 3 H]mevalonate. In addition, huGBPs expressed from the endogenous genes in IFN‐γ‐treated human fibroblasts or monocytic cells were also found to be isoprenoid modified. IFN‐γ‐induced huGBPs in HL‐60 cells were not labeled by the specific C 20 isoprenoid, [ 3 H]geranylgeraniol, but did show decreased isoprenoid incorporation in cells treated with the farnesyl transferase inhibitor BZA5B, indicating that huGBPs in HL‐60 cells are probably modified by a C 15 farnesyl rather than the more common C 20 lipid. Differentiated HL‐60 cells treated with IFN‐γ/LPS showed no change in the profile of constitutive isoprenylated proteins and the IFN‐γ/LPS‐induced huGBPs remained prenylated. Despite being prenylated, huGBP1 in COS cells and endogenous huGBPs in HL‐60 cells were primarily (~85%) cytosolic. Human GBPs are thus among the select group of prenyl proteins whose synthesis is tightly regulated by a cytokine. HuGBP1 is an abundant protein whose prenylation may be vulnerable to farnesyl transferase inhibitors that are designed to prevent farnesylation of Ras proteins. J. Leukoc . Biol . 60: 423–431; 1996.