{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:56:54Z","timestamp":1787587014406,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T00:00:00Z","timestamp":1437436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T00:00:00Z","timestamp":1437436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The phagocyte oxidative burst, mediated by Nox2 NADPH oxidase-derived reactive oxygen species, confers host defense against a broad spectrum of bacterial and fungal pathogens. Loss-of-function mutations that impair function of the Nox2 complex result in a life-threatening immunodeficiency, and genetic variants of Nox2 subunits have been implicated in pathogenesis of inflammatory bowel disease (IBD). Thus, alterations in the oxidative burst can profoundly impact host defense, yet little is known about regulatory mechanisms that fine-tune this response. Here we report the discovery of regulatory nodes controlling oxidative burst by functional screening of genes within loci linked to human inflammatory disease. Implementing a multi-omics approach, we define transcriptional, metabolic and ubiquitin-cycling nodes controlled by<jats:italic>Rbpj, Pfkl<\/jats:italic>and<jats:italic>Rnf145<\/jats:italic>, respectively. Furthermore, we implicate Rnf145 in proteostasis of the Nox2 complex by endoplasmic reticulum-associated degradation. Consequently, ablation of<jats:italic>Rnf145<\/jats:italic>in murine macrophages enhances bacterial clearance, and rescues the oxidative burst defects associated with<jats:italic>Ncf4<\/jats:italic>haploinsufficiency.<\/jats:p>","DOI":"10.1038\/ncomms8838","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T12:12:26Z","timestamp":1437480746000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst"],"prefix":"10.1038","volume":"6","author":[{"given":"Daniel B.","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aivi","family":"Doan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo J.","family":"Villablanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Knights","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Mok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylwin C.Y.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Doench","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Root","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clary B.","family":"Clish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnik J.","family":"Xavier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,21]]},"reference":[{"key":"BFncomms8838_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","volume":"9","author":"TN Mayadas","year":"2013","unstructured":"Mayadas, T. N., Cullere, X. & Lowell, C. A. The multifaceted functions of neutrophils. Annu. Rev. Pathol. 9, 181\u2013218 (2013) .","journal-title":"Annu. Rev. Pathol."},{"key":"BFncomms8838_CR2","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nri3423","volume":"13","author":"C Nathan","year":"2013","unstructured":"Nathan, C. & Cunningham-Bussel, A. Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nat. Rev. Immunol. 13, 349\u2013361 (2013) .","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8838_CR3","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1089\/ars.2006.8.1533","volume":"8","author":"GM Bokoch","year":"2006","unstructured":"Bokoch, G. M. & Zhao, T. Regulation of the phagocyte NADPH oxidase by Rac GTPase. Antioxid. Redox Signal. 8, 1533\u20131548 (2006) .","journal-title":"Antioxid. Redox Signal."},{"key":"BFncomms8838_CR4","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1126\/science.1660188","volume":"254","author":"UG Knaus","year":"1991","unstructured":"Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T. & Bokoch, G. M. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254, 1512\u20131515 (1991) .","journal-title":"Science"},{"key":"BFncomms8838_CR5","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1586\/eri.12.77","volume":"10","author":"J Ben-Ari","year":"2012","unstructured":"Ben-Ari, J., Wolach, O., Gavrieli, R. & Wolach, B. Infections associated with chronic granulomatous disease: linking genetics to phenotypic expression. Expert Rev. Anti Infect. Ther. 10, 881\u2013894 (2012) .","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"BFncomms8838_CR6","doi-asserted-by":"publisher","first-page":"3309","DOI":"10.1182\/blood-2009-07-231498","volume":"114","author":"JD Matute","year":"2009","unstructured":"Matute, J. D. et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood 114, 3309\u20133315 (2009) .","journal-title":"Blood"},{"key":"BFncomms8838_CR7","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1136\/gutjnl-2011-300078","volume":"61","author":"AM Muise","year":"2012","unstructured":"Muise, A. M. et al. NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut 61, 1028\u20131035 (2012) .","journal-title":"Gut"},{"key":"BFncomms8838_CR8","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1053\/j.gastro.2014.06.005","volume":"147","author":"SS Dhillon","year":"2014","unstructured":"Dhillon, S. S. et al. Variants in NADPH oxidase complex components determine susceptibility to very early onset inflammatory bowel disease. Gastroenterology 147, 680\u2013689.e2 (2014) .","journal-title":"Gastroenterology"},{"key":"BFncomms8838_CR9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1600-065X.2009.00841.x","volume":"232","author":"JA Hamerman","year":"2009","unstructured":"Hamerman, J. A., Ni, M., Killebrew, J. R., Chu, C. L. & Lowell, C. A. The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells. Immunol. Rev. 232, 42\u201358 (2009) .","journal-title":"Immunol. Rev."},{"key":"BFncomms8838_CR10","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1172\/JCI32729","volume":"117","author":"DB Graham","year":"2007","unstructured":"Graham, D. B. et al. Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCgamma2 signalling axis in mice. J. Clin. Invest. 117, 3445\u20133452 (2007) .","journal-title":"J. Clin. Invest."},{"key":"BFncomms8838_CR11","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1002\/art.23757","volume":"58","author":"V Cremasco","year":"2008","unstructured":"Cremasco, V., Graham, D. B., Novack, D. V., Swat, W. & Faccio, R. Vav\/Phospholipase Cgamma2-mediated control of a neutrophil-dependent murine model of rheumatoid arthritis. Arthritis. Rheum. 58, 2712\u20132722 (2008) .","journal-title":"Arthritis. Rheum."},{"key":"BFncomms8838_CR12","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1182\/blood-2006-07-033662","volume":"109","author":"AV Miletic","year":"2007","unstructured":"Miletic, A. V. et al. Vav proteins control MyD88-dependent oxidative burst. Blood 109, 3360\u20133368 (2007) .","journal-title":"Blood"},{"key":"BFncomms8838_CR13","doi-asserted-by":"publisher","first-page":"6388","DOI":"10.4049\/jimmunol.177.9.6388","volume":"177","author":"A Utomo","year":"2006","unstructured":"Utomo, A., Cullere, X., Glogauer, M., Swat, W. & Mayadas, T. N. Vav proteins in neutrophils are required for FcgammaR-mediated signalling to Rac GTPases and nicotinamide adenine dinucleotide phosphate oxidase component p40(phox). J. Immunol. 177, 6388\u20136397 (2006) .","journal-title":"J. Immunol."},{"key":"BFncomms8838_CR14","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nature11582","volume":"491","author":"L Jostins","year":"2012","unstructured":"Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119\u2013124 (2012) .","journal-title":"Nature"},{"key":"BFncomms8838_CR15","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.it.2013.04.001","volume":"34","author":"DB Graham","year":"2013","unstructured":"Graham, D. B. & Xavier, R. J. From genetics of inflammatory bowel disease towards mechanistic insights. Trends Immunol. 34, 371\u2013378 (2013) .","journal-title":"Trends Immunol."},{"key":"BFncomms8838_CR16","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/ni.1788","volume":"10","author":"W Wu","year":"2009","unstructured":"Wu, W., Hsu, Y. M., Bi, L., Songyang, Z. & Lin, X. CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex. Nat. Immunol. 10, 1208\u20131214 (2009) .","journal-title":"Nat. Immunol."},{"key":"BFncomms8838_CR17","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1182\/blood.V92.5.1576","volume":"92","author":"KL Anderson","year":"1998","unstructured":"Anderson, K. L., Smith, K. A., Pio, F., Torbett, B. E. & Maki, R. A. Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competent. Blood 92, 1576\u20131585 (1998) .","journal-title":"Blood"},{"key":"BFncomms8838_CR18","doi-asserted-by":"publisher","first-page":"33123","DOI":"10.1074\/jbc.M503401200","volume":"280","author":"A Dominguez-Soto","year":"2005","unstructured":"Dominguez-Soto, A., Puig-Kroger, A., Vega, M. A. & Corbi, A. L. PU.1 regulates the tissue-specific expression of dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin. J. Biol. Chem. 280, 33123\u201333131 (2005) .","journal-title":"J. Biol. Chem."},{"key":"BFncomms8838_CR19","doi-asserted-by":"publisher","first-page":"4742","DOI":"10.1182\/blood-2009-10-249540","volume":"115","author":"CM Krawczyk","year":"2010","unstructured":"Krawczyk, C. M. et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115, 4742\u20134749 (2010) .","journal-title":"Blood"},{"key":"BFncomms8838_CR20","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1182\/blood-2012-03-419747","volume":"120","author":"B Everts","year":"2012","unstructured":"Everts, B. et al. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120, 1422\u20131431 (2012) .","journal-title":"Blood"},{"key":"BFncomms8838_CR21","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1084\/jem.20130252","volume":"210","author":"Z Yang","year":"2013","unstructured":"Yang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J. & Weyand, C. M. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J. Exp. Med. 210, 2119\u20132134 (2013) .","journal-title":"J. Exp. Med."},{"key":"BFncomms8838_CR22","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.abb.2008.12.001","volume":"483","author":"MK Pabarcus","year":"2009","unstructured":"Pabarcus, M. K. et al. CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases. Arch. Biochem. Biophys. 483, 66\u201374 (2009) .","journal-title":"Arch. Biochem. Biophys."},{"key":"BFncomms8838_CR23","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong, L. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339, 819\u2013823 (2013) .","journal-title":"Science"},{"key":"BFncomms8838_CR24","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1232033","volume":"339","author":"P Mali","year":"2013","unstructured":"Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823\u2013826 (2013) .","journal-title":"Science"},{"key":"BFncomms8838_CR25","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1084\/jem.158.3.670","volume":"158","author":"CF Nathan","year":"1983","unstructured":"Nathan, C. F., Murray, H. W., Wiebe, M. E. & Rubin, B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J. Exp. Med. 158, 670\u2013689 (1983) .","journal-title":"J. Exp. Med."},{"key":"BFncomms8838_CR26","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1172\/JCI113153","volume":"80","author":"RA Ezekowitz","year":"1987","unstructured":"Ezekowitz, R. A., Orkin, S. H. & Newburger, P. E. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease. J. Clin. Invest. 80, 1009\u20131016 (1987) .","journal-title":"J. Clin. Invest."},{"key":"BFncomms8838_CR27","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.4049\/jimmunol.157.6.2418","volume":"157","author":"EA Eklund","year":"1996","unstructured":"Eklund, E. A., Luo, W. & Skalnik, D. G. Characterization of three promoter elements and cognate DNA binding protein(s) necessary for IFN-gamma induction of gp91-phox transcription. J. Immunol. 157, 2418\u20132429 (1996) .","journal-title":"J. Immunol."},{"key":"BFncomms8838_CR28","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jprot.2014.03.027","volume":"103","author":"M Depke","year":"2014","unstructured":"Depke, M. et al. Bone marrow-derived macrophages from BALB\/c and C57BL\/6 mice fundamentally differ in their respiratory chain complex proteins, lysosomal enzymes and components of antioxidant stress systems. J. Proteomics 103, 72\u201386 (2014) .","journal-title":"J. Proteomics"},{"key":"BFncomms8838_CR29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature09999","volume":"473","author":"A Klinakis","year":"2011","unstructured":"Klinakis, A. et al. A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473, 230\u2013233 (2011) .","journal-title":"Nature"},{"key":"BFncomms8838_CR30","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/ni.2679","volume":"14","author":"AT Satpathy","year":"2013","unstructured":"Satpathy, A. T. et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat. Immunol. 14, 937\u2013948 (2013) .","journal-title":"Nat. Immunol."},{"key":"BFncomms8838_CR31","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/ni.2304","volume":"13","author":"H Xu","year":"2012","unstructured":"Xu, H. et al. Notch-RBP-J signalling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat. Immunol. 13, 642\u2013650 (2012) .","journal-title":"Nat. Immunol."},{"key":"BFncomms8838_CR32","doi-asserted-by":"publisher","first-page":"e11481","DOI":"10.1371\/journal.pone.0011481","volume":"5","author":"F Meier-Stiegen","year":"2010","unstructured":"Meier-Stiegen, F. et al. Activated Notch1 target genes during embryonic cell differentiation depend on the cellular context and include lineage determinants and inhibitors. PloS ONE 5, e11481 (2010) .","journal-title":"PloS ONE"},{"key":"BFncomms8838_CR33","doi-asserted-by":"publisher","first-page":"e77490","DOI":"10.1371\/journal.pone.0077490","volume":"8","author":"J Dicken","year":"2013","unstructured":"Dicken, J. et al. Transcriptional reprogramming of CD11b(+)Esam(hi) dendritic cell identity and function by loss of Runx3. PloS ONE 8, e77490 (2013) .","journal-title":"PloS ONE"},{"key":"BFncomms8838_CR34","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S0926-6593(65)80213-2","volume":"99","author":"M Zatti","year":"1965","unstructured":"Zatti, M. & Rossi, F. Early changes of hexose monophosphate pathway activity and of NADPH oxidation in phagocytizing leucocytes. Biochim. Biophys. Acta 99, 557\u2013561 (1965) .","journal-title":"Biochim. Biophys. Acta"},{"key":"BFncomms8838_CR35","doi-asserted-by":"publisher","first-page":"40659","DOI":"10.1074\/jbc.M206650200","volume":"277","author":"T Shalom-Barak","year":"2002","unstructured":"Shalom-Barak, T. & Knaus, U. G. A p21-activated kinase-controlled metabolic switch up-regulates phagocyte NADPH oxidase. J. Biol. Chem. 277, 40659\u201340665 (2002) .","journal-title":"J. Biol. Chem."},{"key":"BFncomms8838_CR36","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/ni.2595","volume":"14","author":"A Sokolovska","year":"2013","unstructured":"Sokolovska, A. et al. Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. Nat. Immunol. 14, 543\u2013553 (2013) .","journal-title":"Nat. Immunol."},{"key":"BFncomms8838_CR37","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature13152","volume":"509","author":"R Noubade","year":"2014","unstructured":"Noubade, R. et al. NRROS negatively regulates reactive oxygen species during host defence and autoimmunity. Nature 509, 235\u2013239 (2014) .","journal-title":"Nature"},{"key":"BFncomms8838_CR38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289\u2013300 (1995) .","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"BFncomms8838_CR39","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1373\/clinchem.2012.199133","volume":"59","author":"MK Townsend","year":"2013","unstructured":"Townsend, M. K. et al. Reproducibility of metabolomic profiles among men and women in 2 large cohort studies. Clin. Chem. 59, 1657\u20131667 (2013) .","journal-title":"Clin. Chem."},{"key":"BFncomms8838_CR40","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/nbt1046","volume":"23","author":"J Rush","year":"2005","unstructured":"Rush, J. et al. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. 23, 94\u2013101 (2005) .","journal-title":"Nat. Biotechnol."},{"key":"BFncomms8838_CR41","doi-asserted-by":"publisher","first-page":"19855","DOI":"10.1073\/pnas.0707579104","volume":"104","author":"MP Stokes","year":"2007","unstructured":"Stokes, M. P. et al. Profiling of UV-induced ATM\/ATR signalling pathways. Proc. Natl Acad. Sci. USA 104, 19855\u201319860 (2007) .","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8838_CR42","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.cell.2007.11.025","volume":"131","author":"K Rikova","year":"2007","unstructured":"Rikova, K. et al. Global survey of phosphotyrosine signalling identifies oncogenic kinases in lung cancer. Cell 131, 1190\u20131203 (2007) .","journal-title":"Cell"},{"key":"BFncomms8838_CR43","doi-asserted-by":"publisher","first-page":"ra64","DOI":"10.1126\/scisignal.2000998","volume":"3","author":"A Moritz","year":"2010","unstructured":"Moritz, A. et al. Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. Sci. Signal. 3, ra64 (2010) .","journal-title":"Sci. Signal."},{"key":"BFncomms8838_CR44","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1074\/mcp.M112.027052","volume":"12","author":"F Gnad","year":"2013","unstructured":"Gnad, F. et al. Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics. Mol. Cell. Proteomics 12, 2070\u20132080 (2013) .","journal-title":"Mol. Cell. Proteomics"},{"key":"BFncomms8838_CR45","doi-asserted-by":"publisher","first-page":"41530","DOI":"10.1074\/jbc.M111.248856","volume":"286","author":"KA Lee","year":"2011","unstructured":"Lee, K. A. et al. Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. J. Biol. Chem. 286, 41530\u201341538 (2011) .","journal-title":"J. Biol. Chem."},{"key":"BFncomms8838_CR46","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1021\/ac026117i","volume":"75","author":"J Rappsilber","year":"2003","unstructured":"Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrix-assisted laser desorption\/ionization, nanoelectrospray, and LC\/MS sample pretreatment in proteomics. Anal. Chem. 75, 663\u2013670 (2003) .","journal-title":"Anal. Chem."},{"key":"BFncomms8838_CR47","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1074\/mcp.M111.015883","volume":"11","author":"MP Stokes","year":"2012","unstructured":"Stokes, M. P. et al. PTMScan direct: identification and quantification of peptides from critical signaling proteins by immunoaffinity enrichment coupled with LC-MS\/MS. Mol. Cell. Proteomics 11, 187\u2013201 (2012) .","journal-title":"Mol. Cell. Proteomics"},{"key":"BFncomms8838_CR48","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.jprot.2010.01.011","volume":"73","author":"PC Bonnette","year":"2010","unstructured":"Bonnette, P. C. et al. Phosphoproteomic characterization of PYK2 signalling pathways involved in osteogenesis. J. Proteomics 73, 1306\u20131320 (2010) .","journal-title":"J. Proteomics"},{"key":"BFncomms8838_CR49","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1158\/1535-7163.MCT-10-0976","volume":"10","author":"SR Brave","year":"2011","unstructured":"Brave, S. R. et al. Assessing the activity of cediranib, a VEGFR-2\/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol. Cancer Ther. 10, 861\u2013873 (2011) .","journal-title":"Mol. Cancer Ther."},{"key":"BFncomms8838_CR50","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281\u20132308 (2013) .","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms8838.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8838","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8838.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T03:18:17Z","timestamp":1717989497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms8838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,21]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,24]]}},"alternative-id":["BFncomms8838"],"URL":"https:\/\/doi.org\/10.1038\/ncomms8838","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,21]]},"assertion":[{"value":"2 February 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7838"}}