Activation of the Lck Tyrosine Protein Kinase by the Herpesvirus Saimiri Tip Protein Involves Two Binding Interactions
| Autor: | Peter G. Medveczky, Bartholomew M. Sefton, David A. Hartley, Kambiz Amdjadi, Tamara R. Hurley, Troy C. Lund |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular STAT3 Transcription Factor Herpesvirus saimiri T-Lymphocytes Mutant chemical and pharmacologic phenomena Biology SH3 domain Cell Line Herpesvirus 2 Saimiriine src Homology Domains Jurkat Cells Viral Proteins 03 medical and health sciences In vivo Transcription (biology) Virology Humans Tyrosine Protein kinase A 030304 developmental biology 0303 health sciences Binding Sites 030302 biochemistry & molecular biology hemic and immune systems Biological activity Phosphoproteins Molecular biology Protein Structure Tertiary Cell biology DNA-Binding Proteins Enzyme Activation Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Mutation Trans-Activators biological phenomena cell phenomena and immunity Protein Binding |
| Zdroj: | Virology. 276(2):339-348 |
| ISSN: | 0042-6822 |
| DOI: | 10.1006/viro.2000.0570 |
| Popis: | The Tip protein of Herpesvirus saimiri strain 484C binds to and activates the Lck tyrosine protein kinase. Two sequences in the Tip protein were previously shown to be involved in binding to Lck. A proline-rich region, residues 132–141, binds to the SH3 domain of the Lck protein. We show here that the other Lck-binding domain, residues 104–113, binds to the carboxyl-terminal half of Lck and that this binding does not require the Lck SH3 domain. Mutated Tip containing only one functional Lck-binding domain can bind stably to Lck, although not as strongly as wild-type Tip. Interaction of Tip with Lck through either Lck-binding domain increases the activity of Lck in vivo. Simultaneous binding of both domains is required for maximal activation of Lck. The transient expression of Tip in T cells was found to stimulate both Stat3-dependent and NF-AT-dependent transcription. Mutant forms of Tip lacking one or the other of the two Lck-binding domains retained the ability to stimulate Stat3-dependent transcription. Tip lacking the proline-rich Lck-binding domain exhibited almost wild-type activity in this assay. In contrast, ablation of either Lck-binding domain abolished the ability of Tip to stimulate NF-AT-dependent transcription. Full biological activity of Tip, therefore, appears to require both Lck-binding domains. |
| Databáze: | OpenAIRE |
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