{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:40:49Z","timestamp":1793194849644,"version":"4.5.0"},"reference-count":78,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Several adaptor molecules bind to cytoplasmic tails of \u03b2-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe antithrombotic drugs. We show for the first time that the 14-3-3\u03b6\u2013c-Src\u2013integrin-\u03b23 complex is formed during platelet activation. 14-3-3\u03b6\u2013c-Src interaction is mediated by the -PIRLGLALNFSVFYYE- fragment (PE16) on the 14-3-3\u03b6 and SH2-domain on c-Src, whereas the 14-3-3\u03b6\u2013integrin-\u03b23 interaction is mediated by the -ESKVFYLKMKGDYYRYL- fragment (EL17) on the 14-3-3\u03b6 and -KEATSTF- fragment (KF7) on the \u03b23-integrin cytoplasmic tail. The EL17-motif inhibitor, or KF7 peptide, interferes with the formation of the 14-3-3\u03b6\u2013c-Src\u2013integrin-\u03b23 complex and selectively inhibits \u03b23 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterized a previously unidentified 14-3-3\u03b6\u2013c-Src\u2013integrin-\u03b23 complex in platelets and provided a novel strategy for the development of safe and effective antithrombotic treatments.<\/jats:p>","DOI":"10.1182\/blood.2019002314","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T15:59:53Z","timestamp":1593100793000},"page":"974-988","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":51,"title":["The 14-3-3\u03b6\u2013c-Src\u2013integrin-\u03b23 complex is vital for platelet activation"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-5160","authenticated-orcid":false,"given":"Chuanbin","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjia","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-8503","authenticated-orcid":false,"given":"Gan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"},{"name":"Canadian Blood Services Centre for Innovation, Toronto, ON, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingguo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"},{"name":"Canadian Blood Services Centre for Innovation, Toronto, ON, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mwangi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"},{"name":"University of Chinese Academy of Sciences, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiumin","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilei","family":"Duan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Zohra","family":"Dahmani","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Thomas","family":"Mackeigan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"},{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-2945","authenticated-orcid":false,"given":"Heyu","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Toronto, ON, Canada;"},{"name":"Toronto Platelet Immunobiology Group, Toronto, ON, Canada;"},{"name":"Canadian Blood Services Centre for Innovation, Toronto, ON, Canada;"},{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Lai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioactive Peptides, Yunnan Province\/Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;"},{"name":"Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"3","key":"2020082011245588800_B1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/cvr\/cvu020","article-title":"Inhibiting thrombosis without causing bleeding: can EP3 blockers fulfil the dream?","volume":"101","author":"De Caterina","year":"2014","journal-title":"Cardiovasc Res"},{"issue":"1","key":"2020082011245588800_B2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41467-019-13928-2","article-title":"Structure-guided design of pure orthosteric inhibitors of \u03b1IIb\u03b23 that prevent thrombosis but preserve hemostasis","volume":"11","author":"Adair","year":"2020","journal-title":"Nat Commun"},{"issue":"8","key":"2020082011245588800_B3","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1182\/blood-2008-06-077891","article-title":"The GPIIb\/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend","volume":"112","author":"Coller","year":"2008","journal-title":"Blood"},{"issue":"12","key":"2020082011245588800_B4","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1161\/ATVBAHA.110.207522","article-title":"Signaling during platelet adhesion and activation","volume":"30","author":"Li","year":"2010","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3","key":"2020082011245588800_B5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1473-0502(03)00044-2","article-title":"Platelets in hemostasis and thrombosis: role of integrins and their ligands","volume":"28","author":"Ni","year":"2003","journal-title":"Transfus Apheresis Sci"},{"issue":"11","key":"2020082011245588800_B6","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1074\/mcp.M500209-MCP200","article-title":"The human platelet membrane proteome reveals several new potential membrane proteins","volume":"4","author":"Moebius","year":"2005","journal-title":"Mol Cell Proteomics"},{"issue":"3","key":"2020082011245588800_B7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/0092-8674(91)90458-B","article-title":"Ligands \u201cactivate\u201d integrin \u03b1 IIb \u03b2 3 (platelet GPIIb-IIIa)","volume":"65","author":"Du","year":"1991","journal-title":"Cell"},{"issue":"10","key":"2020082011245588800_B8","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1111\/j.1538-7836.2006.02116.x","article-title":"Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo","volume":"4","author":"Yang","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"3","key":"2020082011245588800_B9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/MOH.0000000000000237","article-title":"Extracellular matrix proteins in the regulation of thrombus formation","volume":"23","author":"Wang","year":"2016","journal-title":"Curr Opin Hematol"},{"issue":"5","key":"2020082011245588800_B10","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1111\/j.1538-7836.2005.01324.x","article-title":"Vitronectin: back into the spotlight","volume":"3","author":"Plow","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"5","key":"2020082011245588800_B11","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1073\/pnas.2628067100","article-title":"Plasma fibronectin promotes thrombus growth and stability in injured arterioles","volume":"100","author":"Ni","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"2020082011245588800_B12","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/j.1538-7836.2005.01217.x","article-title":"Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation","volume":"3","author":"Reheman","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"6","key":"2020082011245588800_B13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.7555\/JBR.29.20150121","article-title":"Platelets in hemostasis and thrombosis: novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis","volume":"29","author":"Hou","year":"2015","journal-title":"J Biomed Res"},{"issue":"pt 2","key":"2020082011245588800_B14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1242\/jcs.041624","article-title":"Mechanisms that regulate adaptor binding to beta-integrin cytoplasmic tails","volume":"122","author":"Legate","year":"2009","journal-title":"J Cell Sci"},{"issue":"2","key":"2020082011245588800_B15","first-page":"162","article-title":"New Concepts and Mechanisms of Platelet Activation Signaling","volume":"32","author":"Estevez","year":"2017","journal-title":"Physiology (Bethesda)"},{"issue":"6","key":"2020082011245588800_B16","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: bidirectional, allosteric signaling machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"issue":"9","key":"2020082011245588800_B17","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1042\/BC20060025","article-title":"Integrin signalling in directed cell migration","volume":"98","author":"Moissoglu","year":"2006","journal-title":"Biol Cell"},{"issue":"7474","key":"2020082011245588800_B18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nature12613","article-title":"A directional switch of integrin signalling and a new anti-thrombotic strategy","volume":"503","author":"Shen","year":"2013","journal-title":"Nature"},{"issue":"5642","key":"2020082011245588800_B19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1126\/science.1086652","article-title":"Talin binding to integrin beta tails: a final common step in integrin activation","volume":"302","author":"Tadokoro","year":"2003","journal-title":"Science"},{"issue":"suppl 1","key":"2020082011245588800_B20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1538-7836.2011.04355.x","article-title":"Molecular mechanism of inside-out integrin regulation","volume":"9","author":"Ye","year":"2011","journal-title":"J Thromb Haemost"},{"issue":"5963","key":"2020082011245588800_B21","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1126\/science.1174779","article-title":"G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin \u201coutside-in\u201d signaling","volume":"327","author":"Gong","year":"2010","journal-title":"Science"},{"issue":"5","key":"2020082011245588800_B22","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.ceb.2012.08.011","article-title":"Inside-out, outside-in, and inside-outside-in: G protein signaling in integrin-mediated cell adhesion, spreading, and retraction","volume":"24","author":"Shen","year":"2012","journal-title":"Curr Opin Cell Biol"},{"issue":"6","key":"2020082011245588800_B23","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1182\/blood-2017-12-820779","article-title":"GPIb\u03b1 is required for platelet-mediated hepatic thrombopoietin generation","volume":"132","author":"Xu","year":"2018","journal-title":"Blood"},{"key":"2020082011245588800_B24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.biocel.2014.07.004","article-title":"A potent anti-thrombosis peptide (vasotab TY) from horsefly salivary glands","volume":"54","author":"Zhang","year":"2014","journal-title":"Int J Biochem Cell Biol"},{"issue":"22","key":"2020082011245588800_B25","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1021\/jm020503a","article-title":"Kinases, homology models, and high throughput docking","volume":"46","author":"Diller","year":"2003","journal-title":"J Med Chem"},{"issue":"3","key":"2020082011245588800_B26","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1182\/blood-2007-09-110437","article-title":"RGT, a synthetic peptide corresponding to the integrin beta 3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin alpha IIb beta 3 with Src kinase","volume":"112","author":"Su","year":"2008","journal-title":"Blood"},{"issue":"1","key":"2020082011245588800_B27","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1038\/s41467-018-05806-0","article-title":"Apolipoprotein A-IV binds \u03b1IIb\u03b23 integrin and inhibits thrombosis","volume":"9","author":"Xu","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"2020082011245588800_B28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1182\/blood-2008-03-145821","article-title":"Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression","volume":"114","author":"Yang","year":"2009","journal-title":"Blood"},{"issue":"4","key":"2020082011245588800_B29","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41590-018-0063-9","article-title":"Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-\u03b2 receptor","volume":"19","author":"Jin","year":"2018","journal-title":"Nat Immunol"},{"issue":"3","key":"2020082011245588800_B30","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/cvr\/cvt276","article-title":"Blocking the EP3 receptor for PGE2 with DG-041 decreases thrombosis without impairing haemostatic competence","volume":"101","author":"Tilly","year":"2014","journal-title":"Cardiovasc Res"},{"issue":"23","key":"2020082011245588800_B31","doi-asserted-by":"crossref","first-page":"13298","DOI":"10.1073\/pnas.2336149100","article-title":"Src kinase activation by direct interaction with the integrin beta cytoplasmic domain","volume":"100","author":"Arias-Salgado","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2020082011245588800_B32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1083\/jcb.200504016","article-title":"Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms","volume":"171","author":"Fagerholm","year":"2005","journal-title":"J Cell Biol"},{"issue":"7","key":"2020082011245588800_B33","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.4049\/jimmunol.154.7.3461","article-title":"Direct interaction of filamin (ABP-280) with the beta 2-integrin subunit CD18","volume":"154","author":"Sharma","year":"1995","journal-title":"J Immunol"},{"issue":"3","key":"2020082011245588800_B34","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1083\/jcb.200703185","article-title":"A molecular switch that controls cell spreading and retraction","volume":"179","author":"Flevaris","year":"2007","journal-title":"J Cell Biol"},{"issue":"38","key":"2020082011245588800_B35","doi-asserted-by":"crossref","first-page":"36323","DOI":"10.1074\/jbc.M304689200","article-title":"The dimeric versus monomeric status of 14-3-3zeta is controlled by phosphorylation of Ser58 at the dimer interface","volume":"278","author":"Woodcock","year":"2003","journal-title":"J Biol Chem"},{"issue":"1","key":"2020082011245588800_B36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev.pharmtox.40.1.617","article-title":"14-3-3 proteins: structure, function, and regulation","volume":"40","author":"Fu","year":"2000","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"25","key":"2020082011245588800_B37","doi-asserted-by":"crossref","first-page":"15825","DOI":"10.1074\/jbc.M115.648428","article-title":"The Tyrosine Kinase c-Src Specifically Binds to the Active Integrin \u03b1IIb\u03b23 to Initiate Outside-in Signaling in Platelets","volume":"290","author":"Wu","year":"2015","journal-title":"J Biol Chem"},{"issue":"5820","key":"2020082011245588800_B38","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1126\/science.1136782","article-title":"Computational design of peptides that target transmembrane helices","volume":"315","author":"Yin","year":"2007","journal-title":"Science"},{"issue":"22","key":"2020082011245588800_B39","doi-asserted-by":"crossref","first-page":"11706","DOI":"10.1074\/jbc.M116.716613","article-title":"Directly Activating the Integrin \u03b1IIb\u03b23 Initiates Outside-In Signaling by Causing \u03b1IIb\u03b23 Clustering","volume":"291","author":"Fong","year":"2016","journal-title":"J Biol Chem"},{"issue":"13","key":"2020082011245588800_B40","doi-asserted-by":"crossref","first-page":"7362","DOI":"10.1074\/jbc.271.13.7362","article-title":"Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha","volume":"271","author":"Du","year":"1996","journal-title":"J Biol Chem"},{"issue":"5","key":"2020082011245588800_B41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/00062752-199704050-00005","article-title":"Structure and function of the glycoprotein Ib-IX-V complex","volume":"4","author":"L\u00f3pez","year":"1997","journal-title":"Curr Opin Hematol"},{"issue":"6","key":"2020082011245588800_B42","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1182\/blood-2005-01-0440","article-title":"A critical role for 14-3-3zeta protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications","volume":"106","author":"Dai","year":"2005","journal-title":"Blood"},{"issue":"22","key":"2020082011245588800_B43","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1182\/blood-2017-09-742650","article-title":"14-3-3 proteins in platelet biology and glycoprotein Ib-IX signaling","volume":"131","author":"Chen","year":"2018","journal-title":"Blood"},{"issue":"12","key":"2020082011245588800_B44","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1161\/CIRCRESAHA.109.204669","article-title":"Identification of a novel 14-3-3zeta binding site within the cytoplasmic domain of platelet glycoprotein Ibalpha that plays a key role in regulating the von Willebrand factor binding function of glycoprotein Ib-IX","volume":"105","author":"Yuan","year":"2009","journal-title":"Circ Res"},{"issue":"47","key":"2020082011245588800_B45","doi-asserted-by":"crossref","first-page":"39474","DOI":"10.1074\/jbc.M504672200","article-title":"Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow","volume":"280","author":"McCarty","year":"2005","journal-title":"J Biol Chem"},{"issue":"9","key":"2020082011245588800_B46","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1161\/ATVBAHA.112.254680","article-title":"ADP-stimulated activation of Akt during integrin outside-in signaling promotes platelet spreading by inhibiting glycogen synthase kinase-3\u03b2","volume":"32","author":"O\u2019Brien","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3","key":"2020082011245588800_B47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nm1722","article-title":"Kindlin-3 is essential for integrin activation and platelet aggregation","volume":"14","author":"Moser","year":"2008","journal-title":"Nat Med"},{"issue":"1","key":"2020082011245588800_B48","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1182\/blood-2007-12-127001","article-title":"Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth","volume":"112","author":"Ono","year":"2008","journal-title":"Blood"},{"issue":"4","key":"2020082011245588800_B49","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1182\/blood-2011-08-372193","article-title":"Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis","volume":"119","author":"Pleines","year":"2012","journal-title":"Blood"},{"issue":"8","key":"2020082011245588800_B50","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/ncb0807-858","article-title":"Functional atlas of the integrin adhesome","volume":"9","author":"Zaidel-Bar","year":"2007","journal-title":"Nat Cell Biol"},{"issue":"7","key":"2020082011245588800_B51","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/(SICI)1521-4141(199907)29:07<2107::AID-IMMU2107>3.0.CO;2-T","article-title":"The cytoskeletal association of CD11\/CD18 leukocyte integrins in phorbol ester-activated cells correlates with CD18 phosphorylation","volume":"29","author":"Valmu","year":"1999","journal-title":"Eur J Immunol"},{"issue":"23","key":"2020082011245588800_B52","doi-asserted-by":"crossref","first-page":"13298","DOI":"10.1073\/pnas.2336149100","article-title":"Src kinase activation by direct interaction with the integrin beta cytoplasmic domain","volume":"100","author":"Arias-Salgado","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"issue":"pt 22","key":"2020082011245588800_B53","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1242\/jcs.00792","article-title":"Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells","volume":"116","author":"Zaidel-Bar","year":"2003","journal-title":"J Cell Sci"},{"issue":"pt 3","key":"2020082011245588800_B54","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1042\/bst0320416","article-title":"Hierarchical assembly of cell-matrix adhesion complexes","volume":"32","author":"Zaidel-Bar","year":"2004","journal-title":"Biochem Soc Trans"},{"issue":"pt 11","key":"2020082011245588800_B55","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1242\/jcs.112.11.1655","article-title":"Molecular diversity of cell-matrix adhesions","volume":"112","author":"Zamir","year":"1999","journal-title":"J Cell Sci"},{"issue":"7","key":"2020082011245588800_B56","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1083\/jcb.153.7.1427","article-title":"Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells","volume":"153","author":"Laukaitis","year":"2001","journal-title":"J Cell Biol"},{"issue":"2","key":"2020082011245588800_B57","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1083\/jcb.200303120","article-title":"Critical roles for the COOH-terminal NITY and RGT sequences of the integrin beta3 cytoplasmic domain in inside-out and outside-in signaling","volume":"162","author":"Xi","year":"2003","journal-title":"J Cell Biol"},{"issue":"2","key":"2020082011245588800_B58","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.drudis.2015.09.012","article-title":"The role of the 14-3-3 protein family in health, disease, and drug development","volume":"21","author":"Aghazadeh","year":"2016","journal-title":"Drug Discov Today"},{"issue":"pt 1","key":"2020082011245588800_B59","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1042\/bj3150041","article-title":"Identification of 14-3-3 proteins in human platelets: effects of synthetic peptides on protein kinase C activation","volume":"315","author":"Wheeler-Jones","year":"1996","journal-title":"Biochem J"},{"issue":"35","key":"2020082011245588800_B60","doi-asserted-by":"crossref","first-page":"33342","DOI":"10.1074\/jbc.M301217200","article-title":"14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac. Platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3 zeta","volume":"278","author":"Bialkowska","year":"2003","journal-title":"J Biol Chem"},{"issue":"13","key":"2020082011245588800_B61","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood-2014-01-453134","article-title":"Src family kinases: at the forefront of platelet activation","volume":"124","author":"Senis","year":"2014","journal-title":"Blood"},{"issue":"4","key":"2020082011245588800_B62","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1073\/pnas.83.4.852","article-title":"Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity","volume":"83","author":"Golden","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2020082011245588800_B63","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nrm2871","article-title":"The final steps of integrin activation: the end game","volume":"11","author":"Shattil","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"2020082011245588800_B64","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1182\/blood-2008-02-140970","article-title":"Src family tyrosine kinase Lyn mediates VWF\/GPIb-IX-induced platelet activation via the cGMP signaling pathway","volume":"112","author":"Yin","year":"2008","journal-title":"Blood"},{"issue":"11","key":"2020082011245588800_B65","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/cncr.24257","article-title":"Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy","volume":"115","author":"Quint\u00e1s-Cardama","year":"2009","journal-title":"Cancer"},{"issue":"9","key":"2020082011245588800_B66","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1182\/blood-2009-02-205328","article-title":"The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo","volume":"114","author":"Gratacap","year":"2009","journal-title":"Blood"},{"issue":"4","key":"2020082011245588800_B67","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000306070","article-title":"A case of acute colitis with severe rectal bleeding in a patient with chronic myeloid leukemia after dasatinib use","volume":"123","author":"Erkut","year":"2010","journal-title":"Acta Haematol"},{"issue":"8","key":"2020082011245588800_B68","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3109\/09537104.2015.1049138","article-title":"Gastrointestinal bleeding in a chronic myeloid leukaemia patient precipitated by dasatinib-induced platelet dysfunction: Case report","volume":"26","author":"Kostos","year":"2015","journal-title":"Platelets"},{"issue":"3","key":"2020082011245588800_B69","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1172\/JCI9896","article-title":"Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen","volume":"106","author":"Ni","year":"2000","journal-title":"J Clin Invest"},{"issue":"21","key":"2020082011245588800_B70","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1056\/NEJMra1601561","article-title":"Von Willebrand\u2019s disease","volume":"375","author":"Leebeek","year":"2016","journal-title":"N Engl J Med"},{"issue":"1","key":"2020082011245588800_B71","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/sj.bjp.0701354","article-title":"Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor","volume":"122","author":"Kageyama","year":"1997","journal-title":"Br J Pharmacol"},{"issue":"2","key":"2020082011245588800_B72","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1160\/TH13-06-0490","article-title":"Anfibatide, a novel GPIb complex antagonist, inhibits platelet adhesion and thrombus formation in vitro and in vivo in murine models of thrombosis","volume":"111","author":"Lei","year":"2014","journal-title":"Thromb Haemost"},{"issue":"2","key":"2020082011245588800_B73","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1161\/hq0202.102321","article-title":"Inhibition of platelet glycoprotein Ib, glycoprotein IIb\/IIIa, or both by monoclonal antibodies prevents arterial thrombosis in baboons","volume":"22","author":"Wu","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"6","key":"2020082011245588800_B74","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/jn\/124.6.825","article-title":"Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women","volume":"124","author":"Xu","year":"1994","journal-title":"J Nutr"},{"issue":"3","key":"2020082011245588800_B75","doi-asserted-by":"crossref","first-page":"E433","DOI":"10.1208\/aapsj080351","article-title":"Pharmacokinetics and bioavailability of the isoflavone biochanin A in rats","volume":"8","author":"Moon","year":"2006","journal-title":"AAPS J"},{"key":"2020082011245588800_B76","first-page":"211","volume-title":"Antioxidant status, diet, nutrition and health","author":"Hendrich","year":"1999"},{"issue":"6","key":"2020082011245588800_B77","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1161\/01.CIR.80.6.1766","article-title":"Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb\/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb\/IIIa receptors","volume":"80","author":"Coller","year":"1989","journal-title":"Circulation"},{"issue":"8","key":"2020082011245588800_B78","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1111\/j.1538-7836.2007.02646.x","article-title":"Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation","volume":"5","author":"Akbar","year":"2007","journal-title":"J Thromb Haemost"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/136\/8\/974\/1755400\/bloodbld2019002314.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/136\/8\/974\/1755400\/bloodbld2019002314.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T19:08:49Z","timestamp":1696273729000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/136\/8\/974\/461127\/The-1433%CE%B6cSrcintegrin%CE%B23-complex-is-vital-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":78,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8,20]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2019002314","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]}}}