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PMID:9218412
| Citation |
Briggs, SD, Sharkey, M, Stevenson, M and Smithgall, TE (1997) SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1. J. Biol. Chem. 272:17899-902 |
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| Abstract |
Tyrosine kinases of the Src family are regulated via their Src homology 2 (SH2) and SH3 domains. The Nef protein of human immunodeficiency virus-1 (HIV-1) has previously been shown to bind with high affinity and specificity in vitro to the SH3 domain of Hck, a Src family member expressed primarily in myeloid cells. However, the effect of Nef on Hck activity in living cells is unknown. Here we show that Rat-2 fibroblasts co-expressing Hck and Nef rapidly developed transformed foci, whereas control cells expressing either protein alone did not. Nef formed a stable complex with Hck and stimulated its tyrosine kinase activity in vivo. Mutagenesis of the Nef proline-rich motif essential for SH3 binding completely blocked complex formation, kinase activation, and transformation, indicating that the Nef SH3-binding function is required for its effects on Hck. These results provide direct evidence that SH3 engagement is sufficient to activate a Src family kinase in vivo and suggest that Hck may be activated by Nef in HIV-infected macrophages. |
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| Keywords |
Animals; Cell Line; Cell Transformation, Neoplastic; Fibroblasts; Gene Products, nef/metabolism; Genetic Vectors; HIV-1/genetics; HIV-1/metabolism; Humans; Mutagenesis, Site-Directed; Phosphorylation; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-hck; Rats; Recombinant Proteins/metabolism; Retroviridae; nef Gene Products, Human Immunodeficiency Virus; src Homology Domains |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0007171 : activation of transmembrane receptor protein tyrosine kinase activity |
ECO:0000314: |
P |
Figure 3 shows that when nef is present with hck it can induce tyrosine phosphorylation of endogenous proteins in wild type cells |
complete | ||||
|
involved_in |
GO:0007171: activation of transmembrane receptor protein tyrosine kinase activity |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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