{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:44:57Z","timestamp":1740145497329,"version":"3.37.3"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:00:00Z","timestamp":1439337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Johns Hopkins University School of Medicine Mass Spectrometry"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To map the phosphoproteome and identify changes in the phosphorylation patterns in the HIV\u2010infected and uninfected brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental design<\/jats:title><jats:p>Parietal cortex from individuals with and without HIV infection were lysed and trypsinized. The peptides were labeled with iTRAQ reagents, combined, phospho\u2010enriched by titanium dioxide chromatography, and analyzed by LC\u2010MS\/MS with high resolution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our phosphoproteomic workflow resulted in the identification of 112 phosphorylated proteins and 17 novel phosphorylation sites in all the samples that were analyzed. The phosphopeptide sequences were searched for kinase substrate motifs, which revealed potential kinases involved in important signaling pathways. The site\u2010specific phosphopeptide quantification showed that peptides from neurofilament medium polypeptide, myelin basic protein, and 2\u2032\u20103\u2032\u2010cyclic nucleotide\u20103\u2032 phosphodiesterase have relatively higher phosphorylation levels during HIV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>This study has enriched the global phosphoproteome knowledge of the human brain by detecting novel phosphorylation sites on neuronal proteins and identifying differentially phosphorylated brain proteins during HIV infection. Kinases that lead to unusual phosphorylations could be therapeutic targets for the treatment of HIV\u2010associated neurocognitive disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.201400134","type":"journal-article","created":{"date-parts":[[2015,5,29]],"date-time":"2015-05-29T18:26:13Z","timestamp":1432923973000},"page":"126-135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mass spectrometric phosphoproteome analysis of HIV\u2010infected brain reveals novel phosphorylation sites and differential phosphorylation patterns"],"prefix":"10.1002","volume":"10","author":[{"given":"Lerna","family":"Uzasci","sequence":"first","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda MD USA"},{"name":"The Department of Pharmacology and Molecular Sciences Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungyoung","family":"Auh","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Cotter","sequence":"additional","affiliation":[{"name":"The Department of Pharmacology and Molecular Sciences Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avindra","family":"Nath","sequence":"additional","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-010-0006-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-014-0263-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2007.08.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr070220c"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr401117m"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-013-9444-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12014-010-9041-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711796150478"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-010-8170-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.14.8130"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1128\/jvi.70.3.1384-1389.1996","article-title":"Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF\u2010kappa B binding and protein kinase C activity in primary human astrocytes","volume":"70","author":"Conant K.","year":"1996","journal-title":"J. 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