Role of Herpes simplex virus 1 VP11/12 tyrosine-based binding motifs for Src family kinases, p85, Grb2 and Shc in activation of the phosphoinositide 3-kinase-Akt pathway
| Autor: | Daniel Gomez Ramos, Holly A. Saffran, James R. Smiley, Ulrike Strunk |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Herpesvirus 1 Human SH2 domain SH3 domain Cell Line Phosphatidylinositol 3-Kinases Viral Proteins 03 medical and health sciences Virology Animals Humans Protein Interaction Domains and Motifs Src family kinase Phosphorylation Antigens Viral Protein kinase B PI3K/AKT/mTOR pathway GRB2 Adaptor Protein biology Akt/PKB signaling pathway Herpes Simplex 3. Good health Cell biology Enzyme Activation src-Family Kinases 030104 developmental biology biology.protein GRB2 biological phenomena cell phenomena and immunity Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists Protein Binding Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Virology. 498:31-35 |
| ISSN: | 0042-6822 |
| Popis: | The abundant HSV-1 tegument protein VP11/12 encoded by gene UL46 is essential for induction of the PI3K/Akt-signaling pathway during infection. VP11/12 utilizes tyrosine-based motifs within its C-terminal region to bind the SH2 domains of Src family kinases, the p85 subunit of PI3 Kinase and Grb2, and the PTB domain of Shc. We previously proposed that the interaction with SFKs and p85 is used to gain control over the PI3K/Akt signaling pathway. We tested this model by evaluating the effects of mutations that eliminate each of these interactions on the ability of HSV-1 to activate Akt. Inhibiting the interaction of VP11/12 with SFKs, p85 and Grb2 reduced Akt activation, while inhibiting the interaction with Shc had little effect. Overall these data support the suggestion that VP11/12 stimulates the PI3K/Akt pathway by mimicking an activated growth factor receptor. |
| Databáze: | OpenAIRE |
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