The phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) binder Rasa3 regulates phosphoinositide 3-kinase (PI3K)-dependent integrin αIIbβ3 outside-in signaling

Journal of Biological Chemistry

Volumn 292, Issue 5, 2017, Pages 1691-1704

  Battram, Anthony M ^a   Durrant, Tom N ^a   Agbani, Ejaife O ^a   Heesom, Kate J ^a   Paul, David S ^b   Piatt, Raymond ^b   Poole, Alastair W ^a   Cullen, Peter J ^a   Bergmeier, Wolfgang ^b   Moore, Samantha F ^a   Hers, Ingeborg ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL MEMBRANES; MAMMALS; PLATELETS;

CELL SPREADING; KEY REGULATORS; LIPID KINASE; MOUSE MODELS; PHOSPHATIDYLINOSITOL; PHOSPHOINOSITIDE 3-KINASE; THROMBOCYTOPENIA; WILD TYPES;

CELL SIGNALING;

ALPHAIIBBETA3 INTEGRIN; FIBRINOGEN; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; INTEGRIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PROTEINASE ACTIVATED RECEPTOR 1; RAP1 PROTEIN; RAS PROTEIN; RASA3 PROTEIN; UNCLASSIFIED DRUG; CELL RECEPTOR; FIBRINOGEN RECEPTOR; INOSITOL-1,3,4,5-TETRAKISPHOSPHATE RECEPTOR; PHOSPHATIDYLINOSITOL 3,4,5-TRIPHOSPHATE; POLYPHOSPHOINOSITIDE; RAP1GAP PROTEIN, HUMAN; RAP1GAP PROTEIN, MOUSE; RASA3 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CELL MEMBRANE; CELL SPREADING; CHO CELL LINE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; GENE MUTATION; GENE TRANSLOCATION; HUMAN; HUMAN CELL; MUTANT; NONHUMAN; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; THROMBOCYTE ACTIVATION; THROMBOCYTOPENIA; WILD TYPE; AMINO ACID SUBSTITUTION; ANIMAL; CRICETULUS; DISEASE MODEL; GENETICS; HAMSTER; METABOLISM; MISSENSE MUTATION; MOUSE; MUTANT MOUSE STRAIN; PATHOLOGY; PHYSIOLOGY; THROMBOCYTE;

AMINO ACID SUBSTITUTION; ANIMALS; BLOOD PLATELETS; CHO CELLS; CRICETINAE; CRICETULUS; DISEASE MODELS, ANIMAL; GTPASE-ACTIVATING PROTEINS; HUMANS; MICE; MICE, MUTANT STRAINS; MUTATION, MISSENSE; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHATIDYLINOSITOL PHOSPHATES; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA;

EID: 85011588725     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.746867     Document Type: Article

References (46)

1. Kucera, G. L., and Rittenhouse, S. E. (1990) Human platelets form 3-phosphorylated phosphoinositides in response to α-thrombin, U46619, or GTPγS. J. Biol. Chem. 265, 5345-5348
2. Jackson, S. P., Schoenwaelder, S. M., Yuan, Y., Rabinowitz, I., Salem, H. H., and Mitchell, C. A. (1994) Adhesion receptor activation of phosphatidylinositol 3-kinase: von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60c-src in human platelets. J. Biol. Chem. 269, 27093-27099
3. Heraud, J. M., Racaud-Sultan, C., Gironcel, D., Albigès-Rizo, C., Giacomini, T., Roques, S., Martel, V., Breton-Douillon, M., Perret, B., and Chap, H. (1998) Lipid products of phosphoinositide 3-kinase and phosphatidylinositol 4, 5-bisphosphate are both required for ADP-dependent platelet spreading. J. Biol. Chem. 273, 17817-17823
4. Canobbio, I., Stefanini, L., Cipolla, L., Ciraolo, E., Gruppi, C., Balduini, C., Hirsch, E., and Torti, M. (2009) Genetic evidence for a predominant role of PI3Kβ catalytic activity in ITAM-and integrin-mediated signaling in platelets. Blood 114, 2193-2196
5. Martin, V., Guillermet-Guibert, J., Chicanne, G., Cabou, C., Jandrot-Perrus, M., Plantavid, M., Vanhaesebroeck, B., Payrastre, B., and Gratacap, M.-P. (2010) Deletion of the p110β isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. Blood 115, 2008-2013
6. Laurent, P.-A., Severin, S., Gratacap, M.-P., and Payrastre, B. (2014) Class I PI 3-kinases signaling in platelet activation and thrombosis: PDK1/Akt/GSK3 axis and impact of PTEN and SHIP1. Adv. Biol. Regul. 54, 162-174
7. Jackson, S. P., Schoenwaelder, S. M., Goncalves, I., Nesbitt, W. S., Yap, C. L., Wright, C. E., Kenche, V., Anderson, K. E., Dopheide, S. M., Yuan, Y., Sturgeon, S. A., Prabaharan, H., Thompson, P. E., Smith, G. D., Shepherd, P. R., et al. (2005) PI 3-kinase p110β: a new target for antithrombotic therapy. Nat. Med. 11, 507-514
8. Stefanini, L., Paul, D. S., Robledo, R. F., Chan, E. R., Getz, T. M., Campbell, R. A., Kechele, D. O., Casari, C., Piatt, R., Caron, K. M., Mackman, N., Weyrich, A. S., Parrott, M. C., Boulaftali, Y., Adams, M. D., et al. (2015) RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J. Clin. Invest. 125, 1419-1432
9. 3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PI 3-kinase. Biochim. Biophys. Acta 1448, 543-552
10. Yi, W., Li, Q., Shen, J., Ren, L., Liu, X., Wang, Q., He, S., Wu, Q., Hu, H., Mao, X., and Zhu, L. (2014) Modulation of platelet activation and thrombus formation using a pan-PI3K inhibitor S14161. PLoS One 9, e102394
11. Gilio, K., Munnix, I. C., Mangin, P., Cosemans, J. M., Feijge, M. A., van der Meijden, P. E., Olieslagers, S., Chrzanowska-Wodnicka, M. B., Lillian, R., Schoenwaelder, S., Koyasu, S., Sage, S. O., Jackson, S. P., and Heemskerk, J. W. (2009) Non-redundant roles of phosphoinositide 3-kinase isoforms α and β in glycoprotein VI-induced platelet signaling and thrombus formation. J. Biol. Chem. 284, 33750-33762
12. Consonni, A., Cipolla, L., Guidetti, G., Canobbio, I., Ciraolo, E., Hirsch, E., Falasca, M., Okigaki, M., Balduini, C., and Torti, M. (2012) Role and regulation of phosphatidylinositol 3-kinase β in platelet integrin α2β1 signaling. Blood 119, 847-856
13. Moore, S. F., Hunter, R. W., Harper, M. T., Savage, J. S., Siddiq, S., Westbury, S. K., Poole, A. W., Mumford, A. D., and Hers, I. (2013) Dysfunction of the PI3 kinase/Rap1/integrin αIIbβ3 pathway underlies ex vivo platelet hypoactivity in essential thrombocythemia. Blood 121, 1209-1219
14. Bertoni, A., Tadokoro, S., Eto, K., Pampori, N., Parise, L. V., White, G. C., and Shattil, S. J. (2002) Relationships between Rap1b, affinity modulation of integrin αIIbβ3 and the actin cytoskeleton. J. Biol. Chem. 277, 25715-25721
15. Chrzanowska-Wodnicka, M., Smyth, S. S., Schoenwaelder, S. M., Fischer, T. H., and White, G. C., 2nd (2005) Rap1b is required for normal platelet function and hemostasis in mice. J. Clin. Invest. 115, 680-687
16. Zhang, G., Xiang, B., Ye, S., Chrzanowska-Wodnicka, M., Morris, A. J., Gartner, T. K., Whiteheart, S. W., White, G. C., 2nd, Smyth, S. S., and Li, Z. (2011) Distinct roles for Rap1b protein in platelet secretion and integrin αIIbβ3 outside-in signaling. J. Biol. Chem. 286, 39466-39477
17. Guidetti, G. F., and Torti, M. (2012) The small GTPase Rap1b: a bidirectional regulator of platelet adhesion receptors. J. Signal Transduct. 2012, 412089
18. Cullen, P. J., Hsuan, J. J., Truong, O., Letcher, A. J., Jackson, T. R., Dawson, A. P., and Irvine, R. F. (1995) Identification of a specific Ins (1, 3, 4, 5) P4-binding protein as a member of the GAP1 family. Nature 376, 527-530
19. Kupzig, S., Deaconescu, D., Bouyoucef, D., Walker, S. A., Liu, Q., Polte, C. L., Daumke, O., Ishizaki, T., Lockyer, P. J., Wittinghofer, A., and Cullen, P. J. (2006) GAP1 family members constitute bifunctional Ras and Rap GTPase-activating proteins. J. Biol. Chem. 281, 9891-9900
20. Molina-Ortiz, P., Polizzi, S., Ramery, E., Gayral, S., Delierneux, C., Oury, C., Iwashita, S., and Schurmans, S. (2014) Rasa3 controls megakaryocyte rap1 activation, integrin signaling and differentiation into proplatelet. PLoS Genet. 10, e1004420
21. Burkhart, J. M., Vaudel, M., Gambaryan, S., Radau, S., Walter, U., Martens, L., Geiger, J., Sickmann, A., and Zahedi, R. P. (2012) The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood 120, e73-e82
22. Rowley, J. W., Oler, A. J., Tolley, N. D., Hunter, B. N., Low, E. N., Nix, D. A., Yost, C. C., Zimmerman, G. A., and Weyrich, A. S. (2011) Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 118, e101-e11
23. Wolthuis, R. M., Franke, B., van Triest, M., Bauer, B., Cool, R. H., Camonis, J. H., Akkerman, J. W., and Bos, J. L. (1998) Activation of the small GTPase Ral in platelets. Mol. Cell Biol. 18, 2486-2491
24. Crittenden, J. R., Bergmeier, W., Zhang, Y., Piffath, C. L., Liang, Y., Wagner, D. D., Housman, D. E., and Graybiel, A. M. (2004) CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat. Med. 10, 982-986
25. Lockyer, P. J., Bottomley, J. R., Reynolds, J. S., McNulty, T. J., Venkateswarlu, K., Potter, B. V., Dempsey, C. E., and Cullen, P. J. (1997) Distinct subcellular localisations of the putative inositol 1, 3, 4, 5-tetrakisphosphate receptors GAP1IP4BP and GAP1m result from the GAP1IP4BP PH domain directing plasma membrane targeting. Curr. Biol. 7, 1007-1010
26. Hammond, G. R., Sim, Y., Lagnado, L., and Irvine, R. F. (2009) Reversible binding and rapid diffusion of proteins in complex with inositol lipids serves to coordinate free movement with spatial information. J. Cell Biol. 184, 297-308
27. Watanabe, N., Bodin, L., Pandey, M., Krause, M., Coughlin, S., Boussiotis, V. A., Ginsberg, M. H., and Shattil, S. J. (2008) Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin αIIbβ3. J. Cell Biol. 181, 1211-1222
28. Kupzig, S., Bouyoucef-Cherchalli, D., Yarwood, S., Sessions, R., and Cullen, P. J. (2009) The ability of GAP1IP4BP to function as a Rap1 GTPaseactivating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb. Mol. Cell Biol. 29, 3929-3940
29. Savage, B., Shattil, S. J., and Ruggeri, Z. M. (1992) Modulation of platelet function through adhesion receptors: a dual role for glycoprotein IIb-IIIa (integrin αIIbβ3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. J. Biol. Chem. 267, 11300-11306
30. Haimovich, B., Lipfert, L., Brugge, J. S., and Shattil, S. J. (1993) Tyrosine phosphorylation and cytoskeletal reorganization in platelets are triggered by interaction of integrin receptors with their immobilized ligands. J. Biol. Chem. 268, 15868-15877
31. Goncalves, I., Hughan, S. C., Schoenwaelder, S. M., Yap, C. L., Yuan, Y., and Jackson, S. P. (2003) Integrin αIIbβ3-dependent calcium signals regulate platelet-fibrinogen interactions under flow: involvement of phospholipase Cγ2. J. Biol. Chem. 278, 34812-34822
32. Blanc, L., Ciciotte, S. L., Gwynn, B., Hildick-Smith, G. J., Pierce, E. L., Soltis, K. A., Cooney, J. D., Paw, B. H., and Peters, L. L. (2012) Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis. Proc. Natl. Acad. Sci. U. S. A. 109, 12099-12104
33. Cullen, P. J., Dawson, A. P., and Irvine, R. F. (1995) Purification and characterization of an Ins (1, 3, 4, 5) P4 binding protein from pig platelets: possible identification of a novel non-neuronal Ins (1, 3, 4, 5) P4 receptor. Biochem. J. 305, 139-143
34. Cozier, G. E., Lockyer, P. J., Reynolds, J. S., Kupzig, S., Bottomley, J. R., Millard, T. H., Banting, G., and Cullen, P. J. (2000) GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association. J. Biol. Chem. 275, 28261-28268
35. Iwashita, S., Kobayashi, M., Kubo, Y., Hinohara, Y., Sezaki, M., Nakamura, K., Suzuki-Migishima, R., Yokoyama, M., Sato, S., Fukuda, M., Ohba, M., Kato, C., Adachi, E., and Song, S.-Y. (2007) Versatile roles of R-Ras GAP in neurite formation of PC12 cells and embryonic vascular development. J. Biol. Chem. 282, 3413-3417
36. Stefanini, L., Boulaftali, Y., Ouellette, T. D., Holinstat, M., Désiré, L., Leblond, B., Andre, P., Conley, P. B., and Bergmeier, W. (2012) Rap1-Rac1 circuits potentiate platelet activation. Arterioscler. Thromb. Vasc. Biol. 32, 434-441
37. Hughes, P. E., Renshaw, M. W., Pfaff, M., Forsyth, J., Keivens, V. M., Schwartz, M. A., and Ginsberg, M. H. (1997) Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell 88, 521-530
38. Shock, D. D., He, K., Wencel-Drake, J. D., and Parise, L. (1997) V Ras activation in platelets after stimulation of the thrombin receptor, thromboxane A2 receptor or protein kinase C. Biochem. J. 321, 525-530
39. Tulasne, D., Bori, T., and Watson, S. P. (2002) Regulation of RAS in human platelets. Evidence that activation of RAS is not sufficient to lead to ERK1-2 phosphorylation. Eur. J. Biochem. 269, 1511-1517
40. Jirousková, M., Jaiswal, J. K., and Coller, B. S. (2007) Ligand density dramatically affects integrin αIIbβ3-mediated platelet signaling and spreading. Blood 109, 5260-5269
41. Canault, M., Ghalloussi, D., Grosdidier, C., Guinier, M., Perret, C., Chelghoum, N., Germain, M., Raslova, H., Peiretti, F., Morange, P. E., Saut, N., Pillois, X., Nurden, A. T., Cambien, F., Pierres, A., et al. (2014) Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding. J. Exp. Med. 211, 1349-1362
42. Lova, P., Paganini, S., Sinigaglia, F., Balduini, C., and Torti, M. (2002) A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets. J. Biol. Chem. 277, 12009-12015
43. Blair, T. A., Moore, S. F., Williams, C. M., Poole, A. W., Vanhaesebroeck, B., and Hers, I. (2014) Phosphoinositide 3-kinases p110α and p110β have differential roles in insulin-like growth factor-1-mediated Akt phosphorylation and platelet priming. Arterioscler. Thromb. Vasc. Biol. 34, 1681-1688
44. Williams, C. M., Harper, M. T., and Poole, A. W. (2014) PKCα negatively regulates in vitro proplatelet formation and in vivo platelet production in mice. Platelets 25, 62-68
45. Goggs, R., Harper, M. T., Pope, R. J., Savage, J. S., Williams, C. M., Mundell, S. J., Heesom, K. J., Bass, M., Mellor, H., and Poole, A. W. (2013) RhoG protein regulates platelet granule secretion and thrombus formation in mice. J. Biol. Chem. 288, 34217-34229
46. Hunter, R. W., Mackintosh, C., and Hers, I. (2009) Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. J. Biol. Chem. 284, 12339-12348