{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:07:39Z","timestamp":1790258859189,"version":"4.1.0"},"reference-count":99,"publisher":"Portland Press Ltd.","issue":"22","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,27]]},"abstract":"<jats:p>Our knowledge on the expression, regulation and roles of the different phosphoinositide 3-kinases (PI3Ks) in platelet signaling and functions has greatly expanded these last twenty years. Much progress has been made in understanding the roles and regulations of class I PI3Ks which produce the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3). Selective pharmacological inhibitors and genetic approaches have allowed researchers to generate an impressive amount of data on the role of class I PI3K\u03b1, \u03b2, \u03b4 and \u03b3 in platelet activation and in thrombosis. Furthermore, platelets do also express two class II PI3Ks (PI3KC2\u03b1 and PI3KC2\u03b2), thought to generate PtdIns(3,4)P2 and PtdIns3P, and the sole class III PI3K (Vps34), known to synthesize PtdIns3P. Recent studies have started to reveal the importance of PI3KC2\u03b1 and Vps34 in megakaryocytes and platelets, opening new perspective in our comprehension of platelet biology and thrombosis. In this review, we will summarize previous and recent advances on platelet PI3Ks isoforms. The implication of these kinases and their lipid products in fundamental platelet biological processes and thrombosis will be discussed. Finally, the relevance of developing potential antithrombotic strategies by targeting PI3Ks will be examined.<\/jats:p>","DOI":"10.1042\/bcj20190402","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T18:55:32Z","timestamp":1606416932000},"page":"4327-4342","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics"],"prefix":"10.1042","volume":"477","author":[{"given":"Agn\u00e8s","family":"Ribes","sequence":"first","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"},{"name":"Laboratoire D'H\u00e9matologie, CHU de Toulouse, 31059 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Oprescu","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Viaud","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Hnia","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebtan","family":"Chicanne","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Xuereb","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Severin","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Gratacap","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-0190","authenticated-orcid":false,"given":"Bernard","family":"Payrastre","sequence":"additional","affiliation":[{"name":"Inserm U1048 and Universit\u00e9 Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France"},{"name":"Laboratoire D'H\u00e9matologie, CHU de Toulouse, 31059 Toulouse Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"2021112218161457700_BCJ-2019-0402CC1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm.2515","article-title":"Arterial thrombosis-insidious, unpredictable and deadly","volume":"17","year":"2011","journal-title":"Nat. Med."},{"key":"2021112218161457700_BCJ-2019-0402CC2","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1056\/NEJMra0801082","article-title":"Mechanisms of thrombus formation","volume":"359","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2021112218161457700_BCJ-2019-0402CC3","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1182\/blood-2013-05-427716","article-title":"Regulation of platelet plug formation by phosphoinositide metabolism","volume":"122","year":"2013","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC4","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/0898-6568(91)90027-r","article-title":"Phosphoinositide 3-kinase: a new effector in signal transduction?","volume":"3","year":"1991","journal-title":"Cell. Signal."},{"key":"2021112218161457700_BCJ-2019-0402CC5","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The phosphoinositide 3-kinase pathway","volume":"296","year":"2002","journal-title":"Science"},{"key":"2021112218161457700_BCJ-2019-0402CC6","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41580-019-0129-z","article-title":"PI3K isoforms in cell signalling and vesicle trafficking","volume":"20","year":"2019","journal-title":"Nat. Rev."},{"key":"2021112218161457700_BCJ-2019-0402CC7","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrm2882","article-title":"The emerging mechanisms of isoform-specific PI3K signalling","volume":"11","year":"2010","journal-title":"Nat. Rev."},{"key":"2021112218161457700_BCJ-2019-0402CC8","doi-asserted-by":"publisher","first-page":"ra89","DOI":"10.1126\/scisignal.2003264","article-title":"G protein-coupled receptor-mediated activation of p110beta by Gbetagamma is required for cellular transformation and invasiveness","volume":"5","year":"2012","journal-title":"Sci. Signal."},{"key":"2021112218161457700_BCJ-2019-0402CC9","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/978-1-4939-2569-8_23","article-title":"Identification of the Rab5 binding site in p110beta: assays for PI3Kbeta binding to Rab5","volume":"1298","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC10","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1042\/BST0340647","article-title":"Signalling through Class I PI3Ks in mammalian cells","volume":"34","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"2021112218161457700_BCJ-2019-0402CC11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1042\/bst0320387","article-title":"Phosphoinositide 3-kinases and the regulation of platelet function","volume":"32","year":"2004","journal-title":"Biochem. Soc. Trans."},{"key":"2021112218161457700_BCJ-2019-0402CC12","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jbior.2013.09.006","article-title":"Class I PI 3-kinases signaling in platelet activation and thrombosis: PDK1\/Akt\/GSK3 axis and impact of PTEN and SHIP1","volume":"54C","year":"2014","journal-title":"Adv. Biol. Regul."},{"key":"2021112218161457700_BCJ-2019-0402CC13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jbior.2015.06.001","article-title":"PI3K\/Akt in platelet integrin signaling and implications in thrombosis","volume":"59","year":"2015","journal-title":"Adv. Biol. Regul."},{"key":"2021112218161457700_BCJ-2019-0402CC14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jbior.2015.11.008","article-title":"The role of class I, II and III PI 3-kinases in platelet production and activation and their implication in thrombosis","volume":"61","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"2021112218161457700_BCJ-2019-0402CC15","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1182\/bloodadvances.2017005173","article-title":"In-depth PtdIns(3,4,5)P3 signalosome analysis identifies DAPP1 as a negative regulator of GPVI-driven platelet function","volume":"1","year":"2017","journal-title":"Blood Adv."},{"key":"2021112218161457700_BCJ-2019-0402CC16","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.bbalip.2018.06.009","article-title":"Profiling of phosphoinositide molecular species in human and mouse platelets identifies new species increasing following stimulation","volume":"1863","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112218161457700_BCJ-2019-0402CC17","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1042\/BST20190205","article-title":"How is the acyl chain composition of phosphoinositides created and does it matter?","volume":"47","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"2021112218161457700_BCJ-2019-0402CC18","doi-asserted-by":"publisher","first-page":"24314","DOI":"10.1074\/jbc.273.38.24314","article-title":"Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets","volume":"273","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC19","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1042\/bj3420171","article-title":"A collagen-related peptide regulates phospholipase Cgamma2 via phosphatidylinositol 3-kinase in human platelets","volume":"342","year":"1999","journal-title":"Biochem. J."},{"key":"2021112218161457700_BCJ-2019-0402CC20","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1182\/blood-2007-02-075432","article-title":"Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLC gamma 2 activation","volume":"110","year":"2007","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC21","doi-asserted-by":"publisher","first-page":"16201","DOI":"10.1074\/jbc.M100873200","article-title":"Interaction between the Btk PH domain and phosphatidylinositol-3,4,5-trisphosphate directly regulates Btk","volume":"276","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC22","doi-asserted-by":"publisher","first-page":"9390","DOI":"10.1073\/pnas.1819301116","article-title":"Structural mechanism for Bruton's tyrosine kinase activation at the cell membrane","volume":"116","year":"2019","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021112218161457700_BCJ-2019-0402CC23","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/S0960-9822(98)70471-3","article-title":"A role for bruton's tyrosine kinase (Btk) in platelet activation by collagen","volume":"8","year":"1998","journal-title":"Curr. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1586\/ehm.09.75","article-title":"Akt signaling in platelets and thrombosis","volume":"3","year":"2010","journal-title":"Expert Rev. Hematol."},{"key":"2021112218161457700_BCJ-2019-0402CC25","doi-asserted-by":"publisher","first-page":"3718","DOI":"10.1182\/blood-2012-10-461897","article-title":"PDK1 regulates platelet activation and arterial thrombosis","volume":"121","year":"2013","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC26","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1080\/09537104.2019.1663806","article-title":"Stimulation of mTORC2 by integrin alphaIIbbeta3 is required for PI3Kbeta-dependent activation of Akt but is dispensable for platelet spreading on fibrinogen","volume":"31","year":"2020","journal-title":"Platelets"},{"key":"2021112218161457700_BCJ-2019-0402CC27","doi-asserted-by":"publisher","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-3beta","volume":"32","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC28","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1182\/blood-2014-07-588335","article-title":"Platelet PI3Kbeta and GSK3 regulate thrombus stability at a high shear rate","volume":"125","year":"2015","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC29","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1182\/blood-2012-04-416594","article-title":"The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways","volume":"120","year":"2012","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC30","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1172\/JCI200420267","article-title":"Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2","volume":"113","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2021112218161457700_BCJ-2019-0402CC31","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1182\/blood-2003-10-3428","article-title":"Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice","volume":"104","year":"2004","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC32","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1182\/blood-2010-12-323204","article-title":"An important role for Akt3 in platelet activation and thrombosis","volume":"118","year":"2011","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC33","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1182\/blood-2009-02-202614","article-title":"A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways","volume":"114","year":"2009","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC34","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1074\/jbc.M116.746867","article-title":"The phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) binder Rasa3 regulates phosphoinositide 3-kinase (PI3K)-dependent integrin alphaIIbbeta3 outside-in signaling","volume":"292","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC35","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1182\/bloodadvances.2018016444","article-title":"ELMO1 deficiency enhances platelet function","volume":"3","year":"2019","journal-title":"Blood Adv."},{"key":"2021112218161457700_BCJ-2019-0402CC36","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/s1097-2765(02)00434-3","article-title":"Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices","volume":"9","year":"2002","journal-title":"Mol. Cell"},{"key":"2021112218161457700_BCJ-2019-0402CC37","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1172\/JCI77993","article-title":"RASA3 is a critical inhibitor of RAP1-dependent platelet activation","volume":"125","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2021112218161457700_BCJ-2019-0402CC38","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1042\/bj20030581","article-title":"SH2-containing inositol 5-phosphatases 1 and 2 in blood platelets: their interactions and roles in the control of phosphatidylinositol 3,4,5-trisphosphate levels","volume":"376","year":"2003","journal-title":"Biochem. J."},{"key":"2021112218161457700_BCJ-2019-0402CC39","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1182\/blood-2010-03-277236","article-title":"PTEN regulates collagen-induced platelet activation","volume":"116","year":"2010","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC40","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.biochi.2015.09.005","article-title":"Phosphoinositides: Important lipids in the coordination of cell dynamics","volume":"125","year":"2016","journal-title":"Biochimie"},{"key":"2021112218161457700_BCJ-2019-0402CC41","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s10555-018-9735-z","article-title":"The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis","volume":"37","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"2021112218161457700_BCJ-2019-0402CC42","doi-asserted-by":"publisher","first-page":"158575","DOI":"10.1016\/j.bbalip.2019.158575","article-title":"Identification of PtdIns(3,4)P2 effectors in human platelets using quantitative proteomics","volume":"1865","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"2021112218161457700_BCJ-2019-0402CC43","doi-asserted-by":"publisher","first-page":"4156","DOI":"10.1182\/blood.V94.12.4156","article-title":"A key role of adenosine diphosphate in the irreversible platelet aggregation induced by the PAR1-activating peptide through the late activation of phosphoinositide 3-kinase","volume":"94","year":"1999","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC44","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S0006-291X(02)00744-1","article-title":"Human platelets contain p110delta phosphoinositide 3-kinase","volume":"296","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112218161457700_BCJ-2019-0402CC45","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/09537100400016711","article-title":"Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in platelets","volume":"16","year":"2005","journal-title":"Platelets"},{"key":"2021112218161457700_BCJ-2019-0402CC46","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1161\/ATVBAHA.118.311410","article-title":"Impact of PI3Kalpha (Phosphoinositide 3-Kinase alpha) inhibition on hemostasis and thrombosis","volume":"38","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC47","doi-asserted-by":"publisher","first-page":"33763","DOI":"10.1074\/jbc.M109.048553","article-title":"Role of phosphoinositide 3-kinase beta in glycoprotein VI-mediated Akt activation in platelets","volume":"284","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC48","doi-asserted-by":"publisher","first-page":"33750","DOI":"10.1074\/jbc.M109.048439","article-title":"Non-redundant roles of phosphoinositide 3-kinase isoforms alpha and beta in glycoprotein VI-induced platelet signaling and thrombus formation","volume":"284","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC49","doi-asserted-by":"publisher","first-page":"4206","DOI":"10.1182\/blood-2007-03-080804","article-title":"Insulin-like growth factor-1 regulates platelet activation through PI3-Kalpha isoform","volume":"110","year":"2007","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC50","doi-asserted-by":"publisher","first-page":"4243","DOI":"10.1182\/blood-2006-10-050633","article-title":"Insulin-like growth factor-1 potentiates platelet activation via the IRS\/PI3Kalpha pathway","volume":"110","year":"2007","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC51","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1161\/ATVBAHA.114.303954","article-title":"Phosphoinositide 3-kinases p110alpha and p110beta have differential roles in insulin-like growth factor-1-mediated Akt phosphorylation and platelet priming","volume":"34","year":"2014","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC52","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.1158\/1078-0432.CCR-16-2888","article-title":"A first-in-human, phase I, dose-escalation study of TAK-117, a selective PI3Kalpha isoform inhibitor, in patients with advanced solid malignancies","volume":"23","year":"2017","journal-title":"Clin Cancer Res."},{"key":"2021112218161457700_BCJ-2019-0402CC53","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1055\/s-0037-1613449","article-title":"A critical role of lipid rafts in the organization of a key FcgammaRIIa-mediated signaling pathway in human platelets","volume":"89","year":"2003","journal-title":"Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC54","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/nm1232","article-title":"PI 3-kinase p110beta: a new target for antithrombotic therapy","volume":"11","year":"2005","journal-title":"Nat. Med."},{"key":"2021112218161457700_BCJ-2019-0402CC55","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.advenzreg.2010.09.011","article-title":"Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions","volume":"51","year":"2011","journal-title":"Adv. Enzyme Regul."},{"key":"2021112218161457700_BCJ-2019-0402CC56","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.18632\/aging.101841","article-title":"Class I PI3Ks in arterial thrombosis","volume":"11","year":"2019","journal-title":"Aging"},{"key":"2021112218161457700_BCJ-2019-0402CC57","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1210\/en.2018-00843","article-title":"PI3Kbeta-a versatile transducer for GPCR, RTK, and small GTPase signaling","volume":"160","year":"2019","journal-title":"Endocrinology"},{"key":"2021112218161457700_BCJ-2019-0402CC58","doi-asserted-by":"publisher","first-page":"ra82","DOI":"10.1126\/scisignal.aae0453","article-title":"Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kbeta in myeloid cells","volume":"9","year":"2016","journal-title":"Sci. Signal."},{"key":"2021112218161457700_BCJ-2019-0402CC59","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1042\/BJ20100166","article-title":"Role of phosphoinositide 3-kinase beta in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways","volume":"429","year":"2010","journal-title":"Biochem. J."},{"key":"2021112218161457700_BCJ-2019-0402CC60","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.1182\/blood-2006-03-006338","article-title":"Continuous signaling via PI3K isoforms beta and gamma is required for platelet ADP receptor function in dynamic thrombus stabilization","volume":"108","year":"2006","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC61","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1182\/blood-2011-07-364992","article-title":"Role and regulation of phosphatidylinositol 3-kinase beta in platelet integrin alpha2beta1 signaling","volume":"119","year":"2012","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC62","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/82_2010_61","article-title":"PI 3-Kinase p110beta regulation of platelet integrin alpha(IIb)beta3","volume":"346","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2021112218161457700_BCJ-2019-0402CC63","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1182\/blood-2009-04-217224","article-title":"Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo","volume":"115","year":"2010","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC64","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1096\/fj.00-0810fje","article-title":"Resistance to thromboembolism in PI3Kgamma-deficient mice","volume":"15","year":"2001","journal-title":"FASEB J."},{"key":"2021112218161457700_BCJ-2019-0402CC65","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1160\/TH05-07-0476","article-title":"Signaling through PI3Kgamma: a common platform for leukocyte, platelet and cardiovascular stress sensing","volume":"95","year":"2006","journal-title":"Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC66","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1182\/blood-2004-05-2005","article-title":"The relative role of PLCbeta and PI3Kgamma in platelet activation","volume":"106","year":"2005","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC67","doi-asserted-by":"publisher","first-page":"28648","DOI":"10.1074\/jbc.M704358200","article-title":"Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets","volume":"282","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021112218161457700_BCJ-2019-0402CC68","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.tibs.2009.02.003","article-title":"Twice upon a time: PI3K's secret double life exposed","volume":"34","year":"2009","journal-title":"Trends Biochem. Sci."},{"key":"2021112218161457700_BCJ-2019-0402CC69","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.cellsig.2018.05.005","article-title":"Phosphoinositide 3-kinase p110alpha negatively regulates thrombopoietin-mediated platelet activation and thrombus formation","volume":"50","year":"2018","journal-title":"Cell. Signal."},{"key":"2021112218161457700_BCJ-2019-0402CC70","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.tcb.2019.01.001","article-title":"Class II PI3K functions in cell biology and disease","volume":"29","year":"2019","journal-title":"Trends Cell Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC71","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1042\/BCJ20160170","article-title":"The intricate regulation and complex functions of the class III phosphoinositide 3-kinase Vps34","volume":"473","year":"2016","journal-title":"Biochem. J."},{"key":"2021112218161457700_BCJ-2019-0402CC72","doi-asserted-by":"publisher","first-page":"100664","DOI":"10.1016\/j.jbior.2019.100664","article-title":"Phosphatidylinositol 3 monophosphate metabolizing enzymes in blood platelet production and in thrombosis","volume":"75","year":"2020","journal-title":"Adv. Biol. Regul."},{"key":"2021112218161457700_BCJ-2019-0402CC73","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/rth2.12321","article-title":"Phosphatidylinositol 3-monophosphate: a novel actor in thrombopoiesis and thrombosis","volume":"4","year":"2020","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC74","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1002\/bies.201300064","article-title":"Phosphatidylinositol 3-phosphate, a lipid that regulates membrane dynamics, protein sorting and cell signalling","volume":"35","year":"2013","journal-title":"Bioessays"},{"key":"2021112218161457700_BCJ-2019-0402CC75","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1111\/jth.14764","article-title":"Vps34 derived phosphatidylinositol 3-monophosphate modulates megakaryocyte maturation and proplatelet production through late endosomes\/lysosomes","volume":"18","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC76","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1042\/BJ20120945","article-title":"A novel mass assay to quantify the bioactive lipid PtdIns3P in various biological samples","volume":"447","year":"2012","journal-title":"Biochem. J."},{"key":"2021112218161457700_BCJ-2019-0402CC77","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1182\/blood-2015-03-636670","article-title":"Essential role of class II PI3K-C2alpha in platelet membrane morphology","volume":"126","year":"2015","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC78","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1182\/blood-2017-04-781641","article-title":"A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth","volume":"130","year":"2017","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC79","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.bbrc.2016.04.127","article-title":"Expression of myotubularins in blood platelets: Characterization and potential diagnostic of X-linked myotubular myopathy","volume":"476","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112218161457700_BCJ-2019-0402CC80","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.1038\/ncomms7535","article-title":"The class II PI 3-kinase, PI3KC2alpha, links platelet internal membrane structure to shear-dependent adhesive function","volume":"6","year":"2015","journal-title":"Nat. Commun."},{"key":"2021112218161457700_BCJ-2019-0402CC81","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/1873-3468.13295","article-title":"The PI 3-kinase PI3KC2alpha regulates mouse platelet membrane structure and function independently of membrane lipid composition","volume":"593","year":"2019","journal-title":"FEBS Lett."},{"key":"2021112218161457700_BCJ-2019-0402CC82","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3109\/09537104.2016.1145202","article-title":"Combined deficiency of PI3KC2alpha and PI3KC2beta reveals a nonredundant role for PI3KC2alpha in regulating mouse platelet structure and thrombus stability","volume":"27","year":"2016","journal-title":"Platelets"},{"key":"2021112218161457700_BCJ-2019-0402CC83","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1161\/ATVBAHA.117.309751","article-title":"Class III PI3K positively regulates platelet activation and thrombosis via PI(3)P-Directed function of NADPH oxidase","volume":"37","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021112218161457700_BCJ-2019-0402CC84","doi-asserted-by":"publisher","first-page":"S313","DOI":"10.1111\/jth.12947","article-title":"Antiplatelet drugs: which targets for which treatments?","volume":"13","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC85","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1182\/blood-2018-02-831982","article-title":"A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding","volume":"132","year":"2018","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC86","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/s0014-5793(03)00337-5","article-title":"A PLC gamma 2-independent platelet collagen aggregation requiring functional association of GPVI and integrin alpha2beta1","volume":"542","year":"2003","journal-title":"FEBS Lett."},{"key":"2021112218161457700_BCJ-2019-0402CC87","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.coph.2015.05.017","article-title":"PI3K inhibitors in inflammation, autoimmunity and cancer","volume":"23","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"2021112218161457700_BCJ-2019-0402CC88","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrclinonc.2013.10","article-title":"Development of PI3K inhibitors: lessons learned from early clinical trials","volume":"10","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2021112218161457700_BCJ-2019-0402CC89","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40169-020-0261-6","article-title":"PI3K inhibitors in thrombosis and cardiovascular disease","volume":"9","year":"2020","journal-title":"Clin Transl. Med."},{"key":"2021112218161457700_BCJ-2019-0402CC90","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1111\/j.1538-7836.2012.04898.x","article-title":"Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor","volume":"10","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC91","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1111\/jth.13027","article-title":"Exploration of efficacy and bleeding with combined phosphoinositide 3-kinase beta inhibition and aspirin in man","volume":"13","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC92","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1111\/j.1538-7836.2012.04912.x","article-title":"Antithrombotic phosphoinositide 3-kinase beta inhibitors in humans: a \u2018shear\u2019 delight!","volume":"10","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC93","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1160\/TH15-08-0661","article-title":"The class I phosphoinositide 3-kinases alpha and beta control antiphospholipid antibodies-induced platelet activation","volume":"115","year":"2016","journal-title":"Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC94","doi-asserted-by":"publisher","first-page":"e38455","DOI":"10.1371\/journal.pone.0038455","article-title":"Combined blockade of ADP receptors and PI3-kinase p110beta fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"2021112218161457700_BCJ-2019-0402CC95","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1160\/TH07-07-0452","article-title":"Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as promising new strategy for platelet protection during extracorporeal circulation","volume":"99","year":"2008","journal-title":"Thromb. Haemost."},{"key":"2021112218161457700_BCJ-2019-0402CC96","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1182\/blood-2014-12-612564","article-title":"PI3Kbeta inhibition: all that glitters is not gold","volume":"125","year":"2015","journal-title":"Blood"},{"key":"2021112218161457700_BCJ-2019-0402CC97","doi-asserted-by":"publisher","first-page":"13536","DOI":"10.1038\/s41598-018-31910-8","article-title":"Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis","volume":"8","year":"2018","journal-title":"Sci. Rep."},{"key":"2021112218161457700_BCJ-2019-0402CC98","doi-asserted-by":"publisher","first-page":"eaar8430","DOI":"10.1126\/scitranslmed.aar8430","article-title":"Disrupting the platelet internal membrane via PI3KC2alpha inhibition impairs thrombosis independently of canonical platelet activation","volume":"12","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"2021112218161457700_BCJ-2019-0402CC99","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1038\/s41467-017-01969-4","article-title":"Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism","volume":"8","year":"2017","journal-title":"Nat. Commun."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/477\/22\/4327\/898105\/bcj-2019-0402c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/477\/22\/4327\/898105\/bcj-2019-0402c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T02:33:07Z","timestamp":1637634787000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/477\/22\/4327\/227054\/Phosphoinositide-3-kinases-in-platelets-thrombosis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,26]]},"references-count":99,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2020,11,27]]}},"URL":"https:\/\/doi.org\/10.1042\/bcj20190402","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,26]]}}}