First Author | Gorbacheva VY | Year | 2002 |
Journal | J Biol Chem | Volume | 277 |
Issue | 8 | Pages | 6080-7 |
PubMed ID | 11726669 | Mgi Jnum | J:74677 |
Mgi Id | MGI:2158961 | Doi | 10.1074/jbc.M110542200 |
Citation | Gorbacheva VY, et al. (2002) The interferon (IFN)-induced GTPase, mGBP-2. Role in IFN-gamma-induced murine fibroblast proliferation. J Biol Chem 277(8):6080-7 |
abstractText | To investigate the function of mGBP-2, a member of the interferon (IFN)-induced guanylate-binding protein family of GTPases, NIH 3T3 fibroblasts were generated that constitutively expressed mGBP-2. mGBP-2 induced a faster growth rate, with the highest expressing clones showing approximately a 50% reduction in doubling time. mGBP-2-expressing cells also grew to higher density and exhibited partial loss of contact growth inhibition, as evidenced by the formation of foci in post-confluent cultures. In addition, mGBP-2-expressing cells showed decreased dependence on serum-derived growth factors. However, they did not lose the requirement for anchorage-dependent growth. Finally, NIH 3T3 cells expressing mGBP-2 formed tumors in athymic mice. An mGBP-2 protein carrying a point mutation (S52N) that reduced GTP binding failed to produce these phenotypes when expressed at the same levels as wild type. The additional finding that IFN-gamma treatment of NIH 3T3 cells resulted in an increase in proliferation similar to that observed for mGBP-2 in the absence of other IFN-induced proteins suggests that mGBP-2 may indeed be important for these growth changes. |