Human cytomegalovirus pUL97 kinase induces global changes in the infected cell phosphoproteome

Adam Oberstein, David H. Perlman, Thomas Shenk, Laura J. Terry

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Replication of human cytomegalovirus (HCMV) is regulated in part by cellular kinases and the single viral Ser/Thr kinase, pUL97. The virus-coded kinase augments the replication of HCMV by enabling nuclear egress and altering cell cycle progression. These roles are accomplished through direct phosphorylation of nuclear lamins and the retinoblastoma protein, respectively. In an effort to identify additional pUL97 substrates, we analyzed the phosphoproteome of SILAC-labeled human fibroblasts during infection with either wild-type HCMV or a pUL97 kinase-dead mutant virus. Phosphopeptides were enriched over a titanium dioxide matrix and analyzed by high-resolution MS. We identified 157 unambiguous phosphosites from 106 cellular and 17 viral proteins whose phosphorylation required UL97. Analysis of peptides containing these sites allowed the identification of several candidate pUL97 phosphorylation motifs, including a completely novel phosphorylation motif, LxSP. Substrates harboring the LxSP motif were enriched in nucleocytoplasmic transport functions, including a number of components of the nuclear pore complex. These results extend the known functions of pUL97 and suggest that modulation of nuclear pore function may be important during HCMV replication.

Original languageEnglish (US)
Pages (from-to)2006-2022
Number of pages17
JournalProteomics
Volume15
Issue number12
DOIs
StatePublished - Jun 1 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Keywords

  • Cell biology
  • Herpesvirus
  • Human cytomegalovirus
  • Nuclear pore complex
  • TREX complex
  • Viral kinase

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