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Among the primate lentiviruses (human immunodeficiency virus
(HIV) -1, HIV-2, and simian immunodeficiency virus (SIV)), the nef gene is highly conserved and encodes a myristylated protein of
Volume 270,
Number 25,
Issue of June 23, pp. 15307-15314, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
27 kDa (HIV-1) or
34 kDa (HIV-2, SIV). Previously, we found
Nef expressed either as a CD8-Nef fusion protein or as a native protein
in virally infected T cell lines associates with a cellular serine
kinase. This kinase activity phosphorylated two proteins of 62 and 72
kDa that coimmunoprecipitate with Nef in in vitro kinase
assays. Using transient expression, various Nef alleles and mutants
have been analyzed for association with the cellular kinase activity.
The ability of Nef to associate with the kinase activity is conserved
among several alleles of HIV-1 as well as SIV
and is
observed in non-lymphoid cell lines of simian and murine origins. Two
separate regions of HIV-1
Nef are critical for the
associated kinase activity. One domain overlaps with a central highly
conserved region found in all primate lentivirus nef genes and
has been provisionally mapped to amino acids 45-127. Because
membrane localization of Nef is important for the associated cellular
kinase activity, the second domain represents a membrane targeting
signal. Moreover, point mutations within the central region that
abrogate the Nef-associated kinase activity in HIV-1
Nef
have the same effect when introduced into SIV
Nef.
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