Nef Binds and activates the Src-family tyrosine kinase Hck

Stable Identifier
R-HSA-200858
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
Compartment
cytosol
ReviewStatus
5/5
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Nef Binds and activates the Src-family tyrosine kinase Hck
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The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a carboxy-terminal site. The SH2 domains of these enzymes play an essential role in this regulation by binding to the tyrosine-phosphorylated tail. The SH2 domain of Hck regulates enzymatic activity indirectly; intramolecular interactions between the SH3 and catalytic domains appear to stabilize an inactive form of the kinase. The HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, binds to either the downregulated or activated form of Hck causing a large increase in Hck catalytic activity. The intact SH3-binding motif in Nef is crucial for Hck activation.
Literature References
PubMed ID Title Journal Year
8599760 The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase

Grzesiek, S, Bax, A, Clore, GM, Gronenborn, AM, Hu, JS, Kaufman, J, Palmer, I, Stahl, SJ, Wingfield, PT

Nat Struct Biol 1996
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

Saksela, K, Cheng, G, Baltimore, D

EMBO J 1995
9024665 Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement

Moarefi, I, LaFevre-Bernt, M, Sicheri, F, Huse, M, Lee, CH, Kuriyan, J, Miller, WT

Nature 1997
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
Human immunodeficiency virus infectious disease DOID:526 HIV infection
Cross References
Mondo
Authored
Gillespie, ME  (2007-07-25)
Reviewed
Skowronski, J  (2007-08-07)
Created
Gillespie, ME  (2007-07-25)
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