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.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Aadra Prashant
authors.initials: AP
authors.lastname: Bhatt
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Jason P
authors.initials: JP
authors.lastname: Wong
authors.affiliation: Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Marc S
authors.initials: MS
authors.lastname: Weinberg
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Kurtis M
authors.initials: KM
authors.lastname: Host
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Louise C
authors.initials: LC
authors.lastname: Giffin
authors.affiliation: Pepscan Presto BV, 8243 Lelystad, The Netherlands;
authors.forename: Joshua
authors.initials: J
authors.lastname: Buijnink
authors.affiliation: Pepscan Presto BV, 8243 Lelystad, The Netherlands;
authors.forename: Evert
authors.initials: E
authors.lastname: van Dijk
authors.affiliation: Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA 95817; Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817;
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumiya
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817;
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; R. L. Juliano Structural Bioinformatics Core Facility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Center for Structural Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Brenda R S
authors.initials: BR
authors.lastname: Temple
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; damania@med.unc.edu.
authors.forename: Blossom
authors.initials: B
authors.lastname: Damania
mesh_terms: D003198:Computer Simulation; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000201:enzymology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008958:Models, Molecular; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: KSHV; ORF36; S6K; cell signaling; viral protein kinase