A viral kinase mimics S6 kinase to enhance cell proliferation

Aadra Prashant Bhatt; Jason P. Wong; Marc S. Weinberg; Kurtis M. Host; Louise C. Giffin; Joshua Buijnink; Evert Van Dijk; Yoshihiro Izumiya; Hsing Jien Kung; Brenda R.S. Temple; Blossom Damania

doi:10.1073/pnas.1600587113

A viral kinase mimics S6 kinase to enhance cell proliferation

Aadra Prashant Bhatt, Jason P. Wong, Marc S. Weinberg, Kurtis M. Host, Louise C. Giffin, Joshua Buijnink, Evert Van Dijk, Yoshihiro Izumiya, Hsing Jien Kung, Brenda R.S. Temple, Blossom Damania

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	7876-7881
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	28
DOIs	https://doi.org/10.1073/pnas.1600587113
Publication status	Published - Jul 12 2016
Externally published	Yes

Keywords

Cell signaling
KSHV
ORF36
S6K
Viral protein kinase

ASJC Scopus subject areas

General

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10.1073/pnas.1600587113

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title = "A viral kinase mimics S6 kinase to enhance cell proliferation",

abstract = "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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author = "Bhatt, {Aadra Prashant} and Wong, {Jason P.} and Weinberg, {Marc S.} and Host, {Kurtis M.} and Giffin, {Louise C.} and Joshua Buijnink and {Van Dijk}, Evert and Yoshihiro Izumiya and Kung, {Hsing Jien} and Temple, {Brenda R.S.} and Blossom Damania",

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doi = "10.1073/pnas.1600587113",

language = "English",

volume = "113",

pages = "7876--7881",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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T1 - A viral kinase mimics S6 kinase to enhance cell proliferation

AU - Bhatt, Aadra Prashant

AU - Wong, Jason P.

AU - Weinberg, Marc S.

AU - Host, Kurtis M.

AU - Giffin, Louise C.

AU - Buijnink, Joshua

AU - Van Dijk, Evert

AU - Izumiya, Yoshihiro

AU - Kung, Hsing Jien

AU - Temple, Brenda R.S.

AU - Damania, Blossom

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

KW - Cell signaling

KW - KSHV

KW - ORF36

KW - S6K

KW - Viral protein kinase

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ER -

A viral kinase mimics S6 kinase to enhance cell proliferation

Abstract

Keywords

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