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Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase\u2013associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in \u03b22 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the \u03b22 integrin cytoplasmic domain, thereby being indispensable for \u03b22 integrin activation and neutrophil recruitment. The direct interaction of Skap2 with the Wiskott\u2013Aldrich syndrome protein via its SH3 domain is critical for integrin activation and neutrophil recruitment in vivo. Furthermore, Skap2 regulates integrin-mediated outside-in signaling events and neutrophil functions. Thus, Skap2 is essential to activate the \u03b22 integrins, and loss of Skap2 function is sufficient to cause a LAD-like phenotype in mice.<\/jats:p>","DOI":"10.1084\/jem.20160647","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T10:20:18Z","timestamp":1486635618000},"page":"851-874","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Skap2 is required for \u03b22 integrin\u2013mediated neutrophil recruitment and functions"],"prefix":"10.1084","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-7722","authenticated-orcid":true,"given":"Mark","family":"Boras","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Volmering","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4238-751X","authenticated-orcid":true,"given":"Arne","family":"Bokemeyer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rossaint","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Block","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Bardel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Van Marck","sequence":"additional","affiliation":[{"name":"Gerhard-Domagk-Institute of Pathology, University Hospital M\u00fcnster, University of M\u00fcnster, 48149 M\u00fcnster, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Heitplatz","sequence":"additional","affiliation":[{"name":"Gerhard-Domagk-Institute of Pathology, University Hospital M\u00fcnster, University of M\u00fcnster, 48149 M\u00fcnster, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kliche","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39106 Magdeburg, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39106 Magdeburg, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford","family":"Lowell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143 4"},{"name":"The Program in Immunology, University of California, San Francisco, San Francisco, CA 94143 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-1714","authenticated-orcid":true,"given":"Alexander","family":"Zarbock","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, and Pain Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"2023072603483735600_bib1","doi-asserted-by":"publisher","first-page":"5535","DOI":"10.1242\/jcs.111260","article-title":"Macrophages require Skap2 and Sirp\u03b1 for integrin-stimulated cytoskeletal rearrangement","volume":"125","author":"Alenghat","year":"2012","journal-title":"J. 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