{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:24:16Z","timestamp":1772018656193,"version":"3.50.1"},"reference-count":42,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,12]]},"abstract":"<jats:p>The invasion of <jats:italic>Toxoplasma gondii<\/jats:italic> tachyzoites into the host cell results in extensive host cell signaling activation\/deactivation that is usually regulated by the phosphorylation\/dephosphorylation. To elucidate how <jats:italic>T. gondii<\/jats:italic> regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture\u2013labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with <jats:italic>T. gondii<\/jats:italic> for different lengths of time (L: 0 hour; M: 2 hours; and H: 6 hours). A total of 892 phosphoproteins were identified with 1,872 phosphopeptides and 1,619 phosphorylation sites. The M versus L comparison revealed 694 significantly regulated phosphopeptides (436 upregulated and 258 downregulated). The H versus L comparison revealed 592 significantly regulated phosphopeptides (146 upregulated and 446 downregulated). The H versus M comparison revealed 794 significantly regulated phosphopeptides (149 upregulated and 645 downregulated). At 2 and 6 hours post-<jats:italic>T. gondii<\/jats:italic> infection, the most predominant host cell reactions were cell cycle regulation and cytoskeletal reorganization, which might be required for the efficient invasion and multiplication of <jats:italic>T. gondii<\/jats:italic>. Similar biological process profiles but different molecular function categories of host cells infected with <jats:italic>T. gondii<\/jats:italic> for 2 and 6 hours, which suggested that the host cell processes were not affected significantly by <jats:italic>T. gondii<\/jats:italic> infection but emphasized some differences in specific cellular processes at this two time points. Western blotting verification of some significantly regulated phosphoprotein phosphorylation sites was consistent with the mass spectra data. This study provided new insights into and further understanding of pathogen\u2013host interactions from the host cell perspective.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0901","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T07:00:06Z","timestamp":1493708406000},"page":"236-244","source":"Crossref","is-referenced-by-count":11,"title":["Phosphoproteome of Toxoplasma gondii Infected Host Cells Reveals Specific Cellular Processes Predominating in Different Phases of Infection"],"prefix":"10.4269","volume":"97","author":[{"given":"Cheng","family":"He","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Xia","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Shuang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Juan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"ref1","series-title":"PLoS Negl Trop Dis","first-page":"e3012","article-title":"Neglected parasitic infections and poverty in the United States","volume":"8","author":"Hotez","year":"2014"},{"key":"ref2","series-title":"Cell Mol Life Sci","first-page":"1900","article-title":"Host cell manipulation by the human pathogen Toxoplasma gondii","volume":"65","author":"Laliberte","year":"2008"},{"key":"ref3","series-title":"Int J Parasitol","first-page":"895","article-title":"Toxoplasmosis: a history of clinical observations","volume":"39","author":"Weiss","year":"2009"},{"key":"ref4","series-title":"J Parasitol","first-page":"620","article-title":"A review: competence, compromise, and concomitance-reaction of the host cell to Toxoplasma gondii infection and development","volume":"97","author":"Peng","year":"2011"},{"key":"ref5","series-title":"Cell","first-page":"635","article-title":"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks","volume":"127","author":"Olsen","year":"2006"},{"key":"ref6","series-title":"Eur J Biochem","first-page":"5001","article-title":"The role of protein phosphorylation in human health and disease. The Sir Hans Krebs Medal Lecture","volume":"268","author":"Cohen","year":"2001"},{"key":"ref7","series-title":"Korean J Parasitol","first-page":"1","article-title":"Anti-apoptotic effects of SERPIN B3 and B4 via STAT6 activation in macrophages after infection with Toxoplasma gondii","volume":"50","author":"Song","year":"2012"},{"key":"ref8","series-title":"Cell Host Microbe","first-page":"208","article-title":"Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses","volume":"8","author":"Peixoto","year":"2010"},{"key":"ref9","series-title":"Cell Microbiol","first-page":"1556","article-title":"Toxoplasma gondii inhibits Fas\/CD95-triggered cell death by inducing aberrant processing and degradation of caspase 8","volume":"9","author":"Vutova","year":"2007"},{"key":"ref10","series-title":"PLoS Pathog","first-page":"e1003779","article-title":"Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways","volume":"9","author":"Melo","year":"2013"},{"key":"ref11","series-title":"Cell Microbiol","first-page":"1153","article-title":"Infection with Toxoplasma gondii results in dysregulation of the host cell cycle","volume":"10","author":"Molestina","year":"2008"},{"key":"ref12","series-title":"PLoS One","first-page":"e10062","article-title":"The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii","volume":"5","author":"Bottova","year":"2010"},{"key":"ref13","series-title":"Biochem Biophys Res Commun","first-page":"656","article-title":"ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion","volume":"378","author":"Da","year":"2009"},{"key":"ref14","series-title":"BMC Microbiol","first-page":"125","article-title":"Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells","volume":"13","author":"Na","year":"2013"},{"key":"ref15","series-title":"Cell Host Microbe","first-page":"410","article-title":"The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries","volume":"10","author":"Treeck","year":"2011"},{"key":"ref16","series-title":"Mol Syst Biol","first-page":"139","article-title":"PhosphoPep-a phosphoproteome resource for systems biology research in Drosophila Kc167 cells","volume":"3","author":"Bodenmiller","year":"2007"},{"key":"ref17","series-title":"Nat Protoc","first-page":"1630","article-title":"The SCX\/IMAC enrichment approach for global phosphorylation analysis by mass spectrometry","volume":"3","author":"Villen","year":"2008"},{"key":"ref18","series-title":"Nat Methods","first-page":"207","article-title":"Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry","volume":"4","author":"Elias","year":"2007"},{"key":"ref19","series-title":"J Proteome Res","first-page":"5354","article-title":"Universal and confident phosphorylation site localization using phosphoRS","volume":"10","author":"Taus","year":"2011"},{"key":"ref20","series-title":"Mol Cell Proteomics","first-page":"1640","article-title":"Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics","volume":"11","author":"Wu","year":"2012"},{"key":"ref21","series-title":"Pharmacol Ther","first-page":"111","article-title":"Protein phosphorylation and signal transduction","volume":"82","author":"Graves","year":"1999"},{"key":"ref22","series-title":"J Cancer Res Clin Oncol","first-page":"744","article-title":"Protein phosphorylation: cellular functions and therapeutic perspectives. Tenth colloquium on cellular signal transduction: DKFZ Heidelberg, 9 February 2001","volume":"127","author":"Marks","year":"2001"},{"key":"ref23","series-title":"Trends Plant Sci","first-page":"54","article-title":"Protein phosphorylation in and around signal transduction","volume":"7","author":"Mundy","year":"2002"},{"key":"ref24","series-title":"Med Chem","first-page":"293","article-title":"Protein phosphorylation and signal transduction modulation: chemistry perspectives for small-molecule drug discovery","volume":"1","author":"Sawyer","year":"2005"},{"key":"ref25","series-title":"J Exp Med","first-page":"2063","article-title":"Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages","volume":"203","author":"Ling","year":"2006"},{"key":"ref26","series-title":"BMC Biol","first-page":"7","article-title":"The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii","volume":"9","author":"Pawlowski","year":"2011"},{"key":"ref27","series-title":"J Biol Chem","first-page":"15611","article-title":"Coordinate control of host centrosome position, organelle distribution, and migratory response by Toxoplasma gondii via host mTORC2","volume":"285","author":"Wang","year":"2010"},{"key":"ref28","series-title":"Science","first-page":"1034","article-title":"Vertebrate cell cycle modulates infection by protozoan parasites","volume":"214","author":"Dvorak","year":"1981"},{"key":"ref29","series-title":"Infect Immun","first-page":"4099","article-title":"Attachment of Toxoplasma gondii to host cells is host cell cycle dependent","volume":"64","author":"Grimwood","year":"1996"},{"key":"ref30","series-title":"Mol Biochem Parasitol","first-page":"95","article-title":"Induction of mitotic S-phase of host and neighboring cells by Toxoplasma gondii enhances parasite invasion","volume":"164","author":"Lavine","year":"2009"},{"key":"ref31","series-title":"Trends Microbiol","first-page":"463","article-title":"Programmed cell death: a fundamental protective response to pathogens","volume":"2","author":"Williams","year":"1994"},{"key":"ref32","series-title":"Immunol Rev","first-page":"5","article-title":"Overview: apoptotic signaling pathways in the immune system","volume":"193","author":"Green","year":"2003"},{"key":"ref33","series-title":"Biochem J","first-page":"333","article-title":"The life of a cell: apoptosis regulation by the PI3K\/PKB pathway","volume":"415","author":"Duronio","year":"2008"},{"key":"ref34","series-title":"Exp Parasitol","first-page":"462","article-title":"Involvement of PI 3 kinase\/Akt-dependent Bad phosphorylation in Toxoplasma gondii-mediated inhibition of host cell apoptosis","volume":"133","author":"Quan","year":"2013"},{"key":"ref35","series-title":"Cell","first-page":"231","article-title":"Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery","volume":"91","author":"Datta","year":"1997"},{"key":"ref36","series-title":"J Theor Biol","first-page":"114","article-title":"The Bcl-2-associated death promoter (BAD) lowers the threshold at which the Bcl-2-interacting domain death agonist (BID) triggers mitochondria disintegration","volume":"271","author":"Howells","year":"2011"},{"key":"ref37","series-title":"Exp Cell Res","first-page":"1444","article-title":"MARCKS is a downstream effector in platelet-derived growth factor-induced cell motility in activated human hepatic stellate cells","volume":"314","author":"Rombouts","year":"2008"},{"key":"ref38","series-title":"Nature","first-page":"320","article-title":"Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane","volume":"351","author":"Thelen","year":"1991"},{"key":"ref39","series-title":"Biochim Biophys Acta","first-page":"837","article-title":"Structural characterization of a neuroblast-specific phosphorylated region of MARCKS","volume":"1844","author":"Tinoco","year":"2014"},{"key":"ref40","series-title":"Dev Biol","first-page":"26","article-title":"Phosphorylated MARCKS: a novel centrosome component that also defines a peripheral subdomain of the cortical actin cap in mouse eggs","volume":"280","author":"Michaut","year":"2005"},{"key":"ref41","series-title":"J Eukaryot Microbiol","first-page":"65","article-title":"Overcoating of Toxoplasma parasitophorous vacuoles with host cell vimentin type intermediate filaments","volume":"41","author":"Halonen","year":"1994"},{"key":"ref42","series-title":"J Biol Chem","first-page":"15278","article-title":"Site-directed spin labeling and electron paramagnetic resonance determination of vimentin head domain structure","volume":"285","author":"Aziz","year":"2010"}],"container-title":["The American Society of Tropical Medicine and 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