Combined deficiency of PI3KC2α and PI3KC2β reveals a nonredundant role for PI3KC2α in regulating mouse platelet structure and thrombus stability

References

• Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol 2010;11(5):329–341.
   PubMed Web of Science ®Google Scholar
• Kok K, Geering B, Vanhaesebroeck B. Regulation of phosphoinositide 3-kinase expression in health and disease. Trends Biochem Sci 2009;34(3):115–127.
   PubMed Web of Science ®Google Scholar
• Markman B, Tao JJ, Scaltriti M. PI3K pathway inhibitors: Better not left alone. Curr Pharmaceut Design 2013;19(5):895–906.
   Google Scholar
• Falasca M, Maffucci T. Regulation and cellular functions of class II phosphoinositide 3-kinases. Biochem J 2012;443(3):587–601.
   PubMed Web of Science ®Google Scholar
• Maffucci T, Falasca M. New insight into the intracellular roles of class II phosphoinositide 3-kinases. Biochem Soc Trans 2014;42(5):1378–1382.
   PubMed Web of Science ®Google Scholar
• Harada K, Truong AB, Cai T, Khavari PA. The class II phosphoinositide 3-kinase C2beta is not essential for epidermal differentiation. Mol Cell Biol 2005;25(24):11122–11130.
   PubMed Web of Science ®Google Scholar
• Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, et al. Endothelial PI3K-C2alpha, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nat Med 2012;18(10):1560–1569.
   PubMed Web of Science ®Google Scholar
• Harris DP, Vogel P, Wims M, Moberg K, Humphries J, Jhaver KG, DaCosta CM, Shadoan MK, Xu N, Hansen GM, et al. Requirement for class II phosphoinositide 3-kinase C2alpha in maintenance of glomerular structure and function. Mol Cell Biol 2011;31(1):63–80.
   PubMed Web of Science ®Google Scholar
• Franco I, Gulluni F, Campa CC, Costa C, Margaria JP, Ciraolo E, Martini M, Monteyne D, De Luca E, Germena G, et al. PI3K class II alpha controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function. Dev Cell 2014;28(6):647–658.
   PubMed Web of Science ®Google Scholar
• Biswas K, Yoshioka K, Asanuma K, Okamoto Y, Takuwa N, Sasaki T, Takuwa Y. Essential role of class II phosphatidylinositol-3-kinase-C2alpha in sphingosine 1-phosphate receptor-1-mediated signaling and migration in endothelial cells. J Biol Chem 2013;288(4):2325–2339.
   PubMed Web of Science ®Google Scholar
• Mountford JK, Petitjean C, Kusuma Putra HK, McCafferty JA, Setiabakti NM, Lee H, Tønnesen LL, McFadyen JD, Schoenwaelder SM, Eckly A, et al. The Class II PI 3-Kinase, PI3KC2α links platelet internal membrane structure to shear-dependent adhesive function. Nat Commun 2015;6:6535.
   PubMed Web of Science ®Google Scholar
• Zhang J, Banfic H, Straforini F, Tosi L, Volinia S, Rittenhouse SE. A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate. J Biol Chem 1998;273(23):14081–14084.
   PubMed Web of Science ®Google Scholar
• Lee H, Sturgeon SA, Jackson SP, Hamilton JR. The contribution of thrombin-induced platelet activation to thrombus growth is diminished under pathological blood shear conditions. Thromb Haemost 2012;107(2):328–337.
   PubMed Web of Science ®Google Scholar
• Ono A, Westein E, Hsiao S, Nesbitt WS, Hamilton JR, Schoenwaelder SM, Jackson SP. Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth. Blood 2008;112(1):90–99.
   PubMed Web of Science ®Google Scholar
• McCormack MP, Hall MA, Schoenwaelder SM, Zhao Q, Ellis S, Prentice JA, Clarke AJ, Slater NJ, Salmon JM, Jackson SP, et al. A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis. Blood 2006;108(7):2248–2256.
   PubMed Web of Science ®Google Scholar
• Stephens LR, Eguinoa A, Erdjument-Bromage H, Lui M, Cooke F, Coadwell J, Smrcka AS, Thelen M, Cadwallader K, Tempst P, Hawkins PT. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell 1997;89(1):105–114.
   PubMed Web of Science ®Google Scholar
• Valet C, Chicanne G, Severac C, Chaussade C, Whitehead MA, Cabou C, Gratacap MP, Gaits-Iacovoni F, Vanhaesebroeck B, Payrastre B, Severin S. Essential role of class II PI3K-C2alpha in platelet membrane morphology. Blood 2015;126(9):1128–1137.
   PubMed Web of Science ®Google Scholar
• Pasquier B, El-Ahmad Y, Filoche-Romme B, Dureuil C, Fassy F, Abecassis PY, Mathieu M, Bertrand T, Benard T, Barrière C, et al. Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)- 3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: A novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J Med Chem 2015;58(1):376–400.
   PubMed Web of Science ®Google Scholar
• Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot MF, Lamberton A, Mathieu M, Bertrand T, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol 2014;10(12):1013–1019.
   PubMed Web of Science ®Google Scholar
• Bago R, Malik N, Munson MJ, Prescott AR, Davies P, Sommer E, Shpiro N, Ward R, Cross D, anley IG, Alessi DR. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem J 2014;463(3):413–427.
   PubMed Web of Science ®Google Scholar
• Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E, Menon S, Wang Z, Honda A, Pardee G, et al. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat Cell Biol 2014;16(11):1069–1079.
   PubMed Web of Science ®Google Scholar
• Dominguez V, Raimondi C, Somanath S, Bugliani M, Loder MK, Edling CE, Divecha N, da Silva-Xavier G, Marselli L, Persaud SJ, et al. Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. J Biol Chem 2011;286(6):4216–4225.
   PubMed Web of Science ®Google Scholar
• Leibiger B, Moede T, Uhles S, Barker CJ, Creveaux M, Domin J, Berggren PO, Leibiger IB. Insulin-feedback via PI3K-C2{alpha} activated PKB{alpha}/Akt1 is required for glucose-stimulated insulin secretion. FASEB J 2010;24(6):1824–1837.
   Google Scholar
• Tibolla G, Pineiro R, Chiozzotto D, Mavrommati I, Wheeler AP, Norata GD, Catapano AL, Maffucci T, Falasca M. Class II phosphoinositide 3-kinases contribute to endothelial cells morphogenesis. PLoS One 2013;8(1):e53808.
   PubMed Web of Science ®Google Scholar