A viral kinase mimics S6 kinase to enhance cell proliferation
| Autor: | Kurtis M. Host, Brenda Temple, Joshua Buijnink, Hsing Jien Kung, Blossom Damania, Marc S. Weinberg, Jason P. Wong, Louise Giffin, Yoshihiro Izumiya, Evert van Dijk, Aadra P. Bhatt |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular P70-S6 Kinase 1 KSHV Biology Mitogen-activated protein kinase kinase MAP2K7 Substrate Specificity ORF36 03 medical and health sciences Viral Proteins Models Human Umbilical Vein Endothelial Cells cell signaling 2.1 Biological and endogenous factors Humans ASK1 Computer Simulation c-Raf Herpesvirus 8 S6K Aetiology Multidisciplinary Ribosomal Protein S6 Kinases Cyclin-dependent kinase 2 Cyclin-dependent kinase 3 Molecular Ribosomal Protein S6 Kinases 70-kDa Biological Sciences Protein kinase R Cell biology viral protein kinase 70-kDa Emerging Infectious Diseases Infectious Diseases 030104 developmental biology HEK293 Cells Herpesvirus 8 Human biology.protein Infection Human |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 113, iss 28 |
| ISSN: | 1091-6490 |
| Popis: | Significance Viruses usurp the host cell machinery to replicate, disseminate, and propagate themselves. Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a viral protein kinase (vPK) also known as ORF36. Using in silico modeling and biochemistry, we report that vPK/ORF36 displays limited homology to cellular S6 kinase B1 (S6KB1). Both kinases share overlapping substrates and can phosphorylate S6. However, unlike S6KB1, vPK augments S6 phosphorylation under conditions where mammalian target of rapamycin (mTOR) is inhibited. vPK modulates cellular proliferation and protein synthesis, augments anchorage independence, and enhances angiogenesis. Depletion of vPK/ORF36 during lytic replication inhibits the production of infectious virions, thereby underscoring the importance of this kinase during the KSHV life cycle. Our collective observations suggest that vPK may function as a constitutively active mimic of S6KB1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|