4.8 Article

A viral kinase mimics S6 kinase to enhance cell proliferation

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1600587113

Keywords

cell signaling; viral protein kinase; S6K; KSHV; ORF36

Funding

  1. NIH [CA096500, CA163217, AI109965, AI107810, DE018281, CA019014, CA14779]
  2. American Cancer Society [RSG-13-383]

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Viruses depend upon the host cell for manufacturing components of progeny virions. To mitigate the inextricable dependence on host cell protein synthesis, viruses can modulate protein synthesis through a variety of mechanisms. We report that the viral protein kinase (vPK) encoded by open reading frame 36 (ORF36) of Kaposi's sarcoma-associated herpesvirus (KSHV) enhances protein synthesis by mimicking the function of the cellular protein S6 kinase (S6KB1). Similar to S6KB1, vPK phosphorylates the ribosomal S6 protein and up-regulates global protein synthesis. vPK also augments cellular proliferation and anchorage-independent growth. Furthermore, we report that both vPK and S6KB1 phosphorylate the enzyme 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) and that both kinases promote endothelial capillary tubule formation.

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