{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:57:53Z","timestamp":1793041073813,"version":"4.5.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T00:00:00Z","timestamp":1368144000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0063152","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T21:09:50Z","timestamp":1368220190000},"page":"e63152","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Activating Mutations in Protein Tyrosine Phosphatase Ptpn11 (Shp2) Enhance Reactive Oxygen Species Production That Contributes to Myeloproliferative Disorder"],"prefix":"10.1371","volume":"8","author":[{"given":"Dan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Mei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Kui","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,5,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10555-008-9126-y","article-title":"The tyrosine phosphatase Shp2 (PTPN11) in cancer","volume":"27","author":"G Chan","year":"2008","journal-title":"Cancer Metastasis Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"4925","DOI":"10.2741\/3051","article-title":"Protein tyrosine phosphatases in the JAK\/STAT pathway","volume":"13","author":"D Xu","year":"2008","journal-title":"Front Biosci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nrm2039","article-title":"Protein tyrosine phosphatases: from genes, to function, to disease","volume":"7","author":"NK Tonks","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/379277a0","article-title":"Spatial constraints on the recognition of phosphoproteins by the tandem SH2 domains of the phosphatase SH-PTP2","volume":"379","author":"MJ Eck","year":"1996","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0092-8674(00)80938-1","article-title":"Crystal structure of the tyrosine phosphatase SHP-2","volume":"92","author":"P Hof","year":"1998","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0969-2126(98)00027-6","article-title":"Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2","volume":"6","author":"D Barford","year":"1998","journal-title":"Structure"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"7335","DOI":"10.1073\/pnas.91.15.7335","article-title":"Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras","volume":"91","author":"AM Bennett","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1128\/MCB.14.1.509","article-title":"A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase","volume":"14","author":"W Li","year":"1994","journal-title":"Mol Cell Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1038\/sj.onc.1206846","article-title":"Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling","volume":"22","author":"WM Yu","year":"2003","journal-title":"Oncogene"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.1128\/MCB.17.9.5499","article-title":"A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development","volume":"17","author":"CK Qu","year":"1997","journal-title":"Mol Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1128\/MCB.18.10.6075","article-title":"Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells","volume":"18","author":"CK Qu","year":"1998","journal-title":"Mol Cell Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1182\/blood.V97.4.911","article-title":"Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development","volume":"97","author":"CK Qu","year":"2001","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1182\/blood-2010-11-319517","article-title":"Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells","volume":"117","author":"G Chan","year":"2011","journal-title":"Blood"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1182\/blood-2011-01-333476","article-title":"Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool","volume":"117","author":"HH Zhu","year":"2011","journal-title":"Blood"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/ng772","article-title":"Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome","volume":"29","author":"M Tartaglia","year":"2001","journal-title":"Nat Genet"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng1156","article-title":"Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia","volume":"34","author":"M Tartaglia","year":"2003","journal-title":"Nat Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1182\/blood-2003-09-3287","article-title":"Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis","volume":"103","author":"ML Loh","year":"2004","journal-title":"Blood"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1182\/blood-2003-11-3876","article-title":"Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia","volume":"104","author":"M Tartaglia","year":"2004","journal-title":"Blood"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/sj.leu.2403492","article-title":"PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children&apos;s Cancer Group","volume":"18","author":"ML Loh","year":"2004","journal-title":"Leukemia"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"8816","DOI":"10.1158\/0008-5472.CAN-04-1923","article-title":"Activating mutations of the noonan syndrome-associated SHP2\/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia","volume":"64","author":"M Bentires-Alj","year":"2004","journal-title":"Cancer Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"30984","DOI":"10.1074\/jbc.M504699200","article-title":"Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes","volume":"280","author":"H Keilhack","year":"2005","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/humu.20005","article-title":"Noonan syndrome-associated SHP2\/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2\/MAPK1 activation","volume":"23","author":"A Fragale","year":"2004","journal-title":"Hum Mutat"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nm1084","article-title":"Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation","volume":"10","author":"T Araki","year":"2004","journal-title":"Nat Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"5426","DOI":"10.1074\/jbc.M507622200","article-title":"Effects of a Leukemia-associated Gain-of-Function Mutation of SHP-2 Phosphatase on Interleukin-3 Signaling","volume":"281","author":"WM Yu","year":"2006","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1074\/jbc.M513068200","article-title":"PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects","volume":"281","author":"MI Kontaridis","year":"2006","journal-title":"J Biol Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ccr.2005.01.010","article-title":"Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations","volume":"7","author":"MG Mohi","year":"2005","journal-title":"Cancer Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1182\/blood-2008-10-182626","article-title":"Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis","volume":"113","author":"G Chan","year":"2009","journal-title":"Blood"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1182\/blood-2010-01-265652","article-title":"A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells","volume":"116","author":"D Xu","year":"2010","journal-title":"Blood"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1084\/jem.20110450","article-title":"Non-lineage\/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on malignant transformation of hematopoietic cells","volume":"208","author":"D Xu","year":"2011","journal-title":"J Exp Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"31107","DOI":"10.1074\/jbc.M200156200","article-title":"Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells","volume":"277","author":"N Chughtai","year":"2002","journal-title":"J Biol Chem"},{"key":"ref31","first-page":"22","article-title":"SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei","volume":"22","author":"TR Wu","year":"2002","journal-title":"J Biol Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"33155","DOI":"10.1074\/jbc.M805138200","article-title":"Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of nuclear export of telomerase reverse transcriptase","volume":"283","author":"S Jakob","year":"2008","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"42812","DOI":"10.1074\/jbc.M305075200","article-title":"DNA damage-induced G2\/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase","volume":"278","author":"L Yuan","year":"2003","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"15208","DOI":"10.1074\/jbc.M211327200","article-title":"Role of SHP-2 tyrosine phosphatase in the DNA damage-induced cell death response","volume":"278","author":"L Yuan","year":"2003","journal-title":"J Biol Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1007\/s00018-004-4211-z","article-title":"Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria","volume":"61","author":"M Salvi","year":"2004","journal-title":"Cell Mol Life Sci"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"24406","DOI":"10.1074\/jbc.M709217200","article-title":"Localization of PTP-1B, SHP-2, and Src exclusively in rat brain mitochondria and functional consequences","volume":"283","author":"A Arachiche","year":"2008","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1073\/pnas.0810053106","article-title":"Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation","volume":"106","author":"T Araki","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1128\/MCB.05629-11","article-title":"A critical role of mitochondrial phosphatase Ptpmt1 in embryogenesis reveals a mitochondrial metabolic stress-induced differentiation checkpoint in embryonic stem cells","volume":"31","author":"J Shen","year":"2011","journal-title":"Mol Cell Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1097-2765(00)80415-3","article-title":"Nf1 and Gmcsf interact in myeloid leukemogenesis","volume":"5","author":"RA Birnbaum","year":"2000","journal-title":"Mol Cell"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1182\/blood-2004-10-4002","article-title":"Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor","volume":"105","author":"RJ Chan","year":"2005","journal-title":"Blood"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"13952","DOI":"10.1074\/jbc.M210670200","article-title":"Development of an efficient \u201csubstrate-trapping\u201d mutant of Src homology phosphotyrosine phosphatase 2 and identification of the epidermal growth factor receptor, Gab1, and three other proteins as target substrates","volume":"278","author":"YM Agazie","year":"2003","journal-title":"J Biol Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.stem.2011.03.009","article-title":"Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging","volume":"8","author":"GL Norddahl","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.stem.2010.07.011","article-title":"The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche","volume":"7","author":"T Simsek","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1182\/blood.V93.9.2928","article-title":"Hematopoietic growth factors signal through the formation of reactive oxygen species","volume":"93","author":"M Sattler","year":"1999","journal-title":"Blood"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1182\/blood.V99.9.3205","article-title":"Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways","volume":"99","author":"JM Carcamo","year":"2002","journal-title":"Blood"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bbadis.2009.10.005","article-title":"A suggested role for mitochondria in Noonan syndrome","volume":"1802","author":"I Lee","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"16421","DOI":"10.1074\/jbc.272.26.16421","article-title":"Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells","volume":"272","author":"H Gu","year":"1997","journal-title":"J Biol Chem"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0063152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T15:45:50Z","timestamp":1595778350000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0063152"}},"subtitle":[],"editor":[{"given":"Kevin D.","family":"Bunting","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,5,10]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,5,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0063152","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,10]]}}}