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Nef Binds and activates the Src-family tyrosine kinase Lck
Stable Identifier
R-HSA-200954
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
Compartment
cytosol
ReviewStatus
5/5
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Disease (Homo sapiens)
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HIV Infection (Homo sapiens)
Host Interactions of HIV factors (Homo sapiens)
The role of Nef in HIV-1 replication and disease pathogenesis (Homo sapiens)
Nef and signal transduction (Homo sapiens)
Nef Binds and activates the Src-family tyrosine kinase Lck (Homo sapiens)
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The Nef protein of the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated protein associated with increased viral replication and enhanced pathogenicity. Both the potentiation of T-lymphocyte activation and the enhanced serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral replication. The Nef proteins from HIV-1 and SIV bind to Lck. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with non-tyrosine-phosphorylated Nef proteins. The conserved core region of HIV-1 Nef is essential for the interaction with Lck and is also important for enhanced HIV-1 replication in T-lymphocytes. The SIV and HIV-1 Nef proteins are differentially tyrosine-phosphorylated. The kinase-active Lck tyrosine-phosphorylates SIVmac239 Nef but does not phosphorylate HIV-1 Nef.
Literature References
PubMed ID
Title
Journal
Year
10544125
The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes
Parks, WP
,
Hoxie, JP
,
Cheng, H
Virology
1999
7859737
Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4
Baltimore, D
,
Cheng, G
,
Saksela, K
EMBO J
1995
Participants
Input
LCK [cytosol]
(Homo sapiens)
myristoylated nef [cytosol]
(Human immunodeficiency virus 1)
Output
Lck:Nef [cytosol]
(Homo sapiens)
Participates
as an event of
Nef and signal transduction (Homo sapiens)
Disease
Name
Identifier
Synonyms
Human immunodeficiency virus infectious disease
DOID:526
HIV infection
Authored
Gillespie, ME (2007-07-25)
Reviewed
Skowronski, J (2007-08-07)
Created
Gillespie, ME (2007-07-26)
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