{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:21:27Z","timestamp":1790050887137,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>Kindlin-3 is a critical supporter of integrin function in platelets. Lack of expression of kindlin-3 protein in patients impairs integrin \u03b1IIb\u03b23\u2013mediated platelet aggregation. Although kindlin-3 has been categorized as an integrin-binding partner, the functional significance of the direct interaction of kindlin-3 with integrin \u03b1IIb\u03b23 in platelets has not been established. Here, we evaluated the significance of the binding of kindlin-3 to integrin \u03b1IIb\u03b23 in platelets in supporting integrin \u03b1IIb\u03b23\u2013mediated platelet functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>We generated a strain of kindlin-3 knockin (K3KI) mice that express a kindlin-3 mutant that carries an integrin-interaction defective substitution. K3KI mice could survive normally and express integrin \u03b1IIb\u03b23 on platelets similar to their wild-type counterparts. Functional analysis revealed that K3KI mice exhibited defective platelet function, including impaired integrin \u03b1IIb\u03b23 activation, suppressed platelet spreading and platelet aggregation, prolonged tail bleeding time, and absence of platelet-mediated clot retraction. In addition, whole blood drawn from K3KI mice showed resistance to in vitro thrombus formation and, as a consequence, K3KI mice were protected from in vivo arterial thrombosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>These observations demonstrate that the direct binding of kindlin-3 to integrin \u03b1IIb\u03b23 is involved in supporting integrin \u03b1IIb\u03b23 activation and integrin \u03b1IIb\u03b23-dependent responses of platelets and consequently contributes significantly to arterial thrombus formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303851","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T22:26:07Z","timestamp":1403821567000},"page":"1961-1967","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Direct Interaction of Kindlin-3 With Integrin \u03b1IIb\u03b23 in Platelets Is Required for Supporting Arterial Thrombosis in Mice"],"prefix":"10.1161","volume":"34","author":[{"given":"Zhen","family":"Xu","sequence":"first","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Zhi","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Bialkowska","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana V.","family":"Byzova","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Pluskota","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Gilbert C.","family":"White","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"Plow","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"From the Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China (Z.X., J.G., E.F.P., Y.-Q.M.); Blood Research Institute, Blood Center of Wisconsin, Milwaukee (Z.X., H.Z., G.C.W., Y.-Q.M.); Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (X.C., J.L.); and Department of Molecular Cardiology, Cleveland Clinic, OH (K.B., T.V.B., E.P., E.F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-077891"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.300570"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03397.x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2009.07.006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-239269"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04355.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086652"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.06.011"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2013.05.014"},{"key":"e_1_3_4_11_2","first-page":"579","article-title":"Mechanisms of talin-dependent integrin signaling and crosstalk.","volume":"0838","author":"Das M","year":"2013","unstructured":"Das M, Subbayya IS, Qin J, Plow EF. Mechanisms of talin-dependent integrin signaling and crosstalk. Biochim Biophys Acta. 2013;0838:579\u2013588.","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611680200"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200710196"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1722"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.202"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e32832ea389"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.336743"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.06.030"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-163162"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1917"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1931"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-182154"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2011.10.004"},{"key":"e_1_3_4_24_2","first-page":"16","article-title":"Lessons from rare maladies: leukocyte adhesion deficiency syndromes.","volume":"20","author":"Harris ES","year":"2013","unstructured":"Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20:16\u201325.","journal-title":"Curr Opin Hematol"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04768.x"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1921"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.033"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809233200"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-520627"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.09.050"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-497669"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.03.086"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443325"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200303120"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02537.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00640.x"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12613"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.114.303851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T18:53:40Z","timestamp":1715540020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.114.303851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1161\/ATVBAHA.114.303851"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.114.303851","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718470378.793498007","asserted-by":"object"}]},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9]]},"assertion":[{"value":"2014-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}