{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T01:38:52Z","timestamp":1778809132893,"version":"3.51.4"},"reference-count":44,"publisher":"Proceedings of the National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,4,25]]},"abstract":"<jats:p>A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes &gt;96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>production in an<jats:italic>in vitro<\/jats:italic>assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2<jats:sup>D57N<\/jats:sup>). Asp57 is invariant in all defined GTP-binding proteins. Rac2<jats:sup>D57N<\/jats:sup>binds GDP but not GTP and inhibits oxidase activation and O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>production<jats:italic>in vitro<\/jats:italic>. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.<\/jats:p>","DOI":"10.1073\/pnas.080074897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:38:21Z","timestamp":1027694301000},"page":"4654-4659","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":388,"title":["Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation"],"prefix":"10.1073","volume":"97","author":[{"given":"Daniel R.","family":"Ambruso","sequence":"first","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Cindy","family":"Knall","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Amy N.","family":"Abell","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Julie","family":"Panepinto","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Arlet","family":"Kurkchubasche","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Gail","family":"Thurman","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Carolina","family":"Gonzalez-Aller","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Andrew","family":"Hiester","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Martin","family":"deBoer","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Ronald J.","family":"Harbeck","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Ryan","family":"Oyer","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Gary L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]},{"given":"Dirk","family":"Roos","sequence":"additional","affiliation":[{"name":"Bonfils Blood Center, Denver, CO 80220; Department of Pediatrics, and Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262; Departments of Pediatric Hematology\/Oncology and Surgery, Rhode Island Hospital, Providence, RI 02903; Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands; and Clinical Labs, National Jewish Medical and Research Center, Denver, CO 80206"}]}],"member":"341","published-online":{"date-parts":[[2000,4,11]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"The Neutrophil: Functions and Clinical Disorders","author":"Klebanoff S J","year":"1978","unstructured":"S J Klebanoff, R A Clark The Neutrophil: Functions and Clinical Disorders (Elsevier, Amsterdam, 1978)."},{"key":"e_1_3_3_2_2","volume-title":"The Molecular Basis of Blood Diseases","author":"Curnutte J","year":"1994","unstructured":"J Curnutte, S Orkin, M Dinauer The Molecular Basis of Blood Diseases, ed G Stamatoyannapoulos (Saunders, 2nd Ed., Philadelphia, 1994).","edition":"2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199704010-00003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1660188"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.11.4366"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.11.4321.bloodjournal88114321"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)40138-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00915283"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4049\/jimmunol.124.2.855","volume":"124","author":"Bentwood B J","year":"1980","unstructured":"B J Bentwood, P M Henson J Immunol 124, 855\u2013862 (1980).","journal-title":"J Immunol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.74.1.75"},{"key":"e_1_3_3_11_2","first-page":"377","volume":"27","author":"Keller H U","year":"1977","unstructured":"H U Keller, P C Wilkinson, M Abercrombie, E L Becker, J G Hirsch, M E Miller, W Scottramsey, S H Zigmond Clin Exp Immunol 27, 377\u2013380 (1977).","journal-title":"Clin Exp Immunol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)55064-X"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00211a050"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8775"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18834"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90358-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.38.020187.001135"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.5.1037.1037"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.5.1663.1663"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111884"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35877-0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36882-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47341-3"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80837-X"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/353668a0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/349117a0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/348125a0"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.6.3707-3718.1994"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54022-9"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/371164a0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(96)10026-X"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.5.1649.bloodjournal8651649"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.509"},{"key":"e_1_3_3_35_2","first-page":"109","volume":"5","author":"Zigmond S H","year":"1996","unstructured":"S H Zigmond Curr Opin Cell Biol 5, 109\u2013113 (1996).","journal-title":"Curr Opin Cell Biol"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.18.2295"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36716-X"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80019-9"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8036496"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00249a031"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.2.363"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5251.981"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.5.1147"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.9.1487"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.080074897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T12:18:58Z","timestamp":1682165938000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.080074897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,4,11]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2000,4,25]]}},"alternative-id":["10.1073\/pnas.080074897"],"URL":"https:\/\/doi.org\/10.1073\/pnas.080074897","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,4,11]]},"assertion":[{"value":"1999-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}