{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:55:22Z","timestamp":1791219322140,"version":"4.1.0"},"reference-count":110,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>3BP2 is a pleckstrin homology and Src homology 2 domain-containing adapter protein mutated in cherubism, a rare autosomal-dominant human bone disorder. Previously, we have demonstrated a functional role for 3BP2 in peripheral B cell development and in peritoneal B1 and splenic marginal zone B cell-mediated Ab responses. In this study, we show that 3BP2 is required for G protein-coupled receptor-mediated neutrophil functions. Neutrophils derived from 3BP2-deficient (Sh3bp2\u2212\/\u2212) mice failed to polarize their actin cytoskeleton or migrate in response to a gradient of chemotactic peptide, fMLF. Sh3bp2\u2212\/\u2212 neutrophils failed to adhere, crawl, and emigrate out of the vasculature in response to fMLF superfusion. 3BP2 is required for optimal activation of Src family kinases, small GTPase Rac2, neutrophil superoxide anion production, and for Listeria monocytogenes bacterial clearance in vivo. The functional defects observed in Sh3bp2\u2212\/\u2212 neutrophils may partially be explained by the failure to fully activate Vav1 guanine nucleotide exchange factor and properly localize P-Rex1 guanine nucleotide exchange factor at the leading edge of migrating cells. Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function.<\/jats:p>","DOI":"10.4049\/jimmunol.1103184","type":"journal-article","created":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T12:00:22Z","timestamp":1342699222000},"page":"2138-2150","source":"Crossref","is-referenced-by-count":22,"title":["The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation"],"prefix":"10.1093","volume":"189","author":[{"given":"Grace","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 148,","place":["Canada"]},{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Dimitriou","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 148,","place":["Canada"]},{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Milne","sequence":"additional","affiliation":[{"name":"Immunology Research Group, Department of Physiology and Biophysics, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta T2N 4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University , 40225 Duesseldorf,","place":["Germany"]},{"name":"Institute for Immunology, University of Essen , 45147 Essen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A","family":"Lang","sequence":"additional","affiliation":[{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]},{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University , 40225 Duesseldorf,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Fine","sequence":"additional","affiliation":[{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]},{"name":"Department of Medical Biophysics, University of Toronto , Toronto, Ontario M5G 2M9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 148,","place":["Canada"]},{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]},{"name":"Department of Medical Biophysics, University of Toronto , Toronto, Ontario M5G 2M9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kubes","sequence":"additional","affiliation":[{"name":"Immunology Research Group, Department of Physiology and Biophysics, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta T2N 4N1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rottapel","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 148,","place":["Canada"]},{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network , Toronto, Ontario M5G 2C1,","place":["Canada"]},{"name":"Department of Medical Biophysics, University of Toronto , Toronto, Ontario M5G 2M9,","place":["Canada"]},{"name":"Department of Medicine, University of Toronto , Toronto, Ontario M5G 2C4,","place":["Canada"]},{"name":"St. Michael\u2019s Hospital , Toronto, Ontario M5B 1W8,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,1]]},"reference":[{"key":"2025032409230282200_r1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.bioeng.7.060804.100423","article-title":"Molecular mechanics and dynamics of leukocyte recruitment during inflammation","volume":"7","author":"Simon","year":"2005","journal-title":"Annu. 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