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1
*
Institute for Genetics, University of Cologne, Cologne, Germany; and
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
IFN-
induces a number of cellular programs functional in innate
and adaptive resistance to infectious pathogens. It has recently become
clear that the complete cellular response to IFN- is extraordinarily
complex, with >500 genes (i.e., 
0.5% of the genome) activated. We
made suppression-subtractive hybridization differential libraries from
IFN--stimulated primary mouse embryonic fibroblasts and from a mouse
macrophage cell line, ANA-1, in each case with reference to
unstimulated cells. Of 250 clones sequenced at random from the two
libraries, >35% were representatives of one or the other of two small
unrelated families of GTPases, the 65-kDa and 47-kDa families. These
families dominate the IFN--induced response in both cell types. We
report here the full-length sequences of one new 65-kDa and two new
47-kDa family members. The 65-kDa family members are under
transcriptional control of IRF-1, whereas the 47-kDa family members are
inducible in embryonic fibroblasts from IRF-1-/- mice.
Members of both GTPase families are strongly up-regulated in livers of
wild-type mice infected with the pathogenic bacterium, Listeria
monocytogenes, but not in IFN-R0/0 mice. These
GTPases appear to be dedicated to the IFN- response, since resting
levels are negligible and since neither family shows any significant
relationship to any other described family of GTPases. Understanding
the role of these GTPases in IFN--mediated resistance against
pathogens is the task for the future.
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