Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
Open accessAbstract
The growth arrest-specific gene 6 product (Gas6) is a secreted protein related to the anticoagulant protein S but its role in hemostasis is unknown. Here we show that inactivation of the Gas6 gene prevented venous and arterial thrombosis in mice, and protected against fatal collagen/epinephrine-induced thrombo embolism. Gas6-/- mice did not, however, suffer spontaneous bleeding and had normal bleeding after tail clipping. In addition, we found that Gas6 antibodies inhibited platelet aggregation in vitro and protected mice against fatal thrombo embolism without causing bleeding in vivo. Gas6 amplified platelet aggregation and secretion in response to known agonists. Platelet dysfunction in Gas6-/- mice resembled that of patients with platelet signaling transduction defects. Thus, Gas6 is a platelet-response amplifier that plays a significant role in thrombosis. These findings warrant further evaluation of the possible therapeutic use of Gas6 inhibition for prevention of thrombosis.
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Genes specifically expressed at growth arrest of mammalian cells
Schneider, C., King, R. M., & Philipson, L. (1988) · Cell · doi:10.1016/s0092-8674(88)91065-3 · Cited by 989 · see citing works
Dahlbäck, B. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02225-x · Cited by 613 · see citing works
Self-citationManfioletti, G., Brancolini, C., Avanzi, G. C., & Schneider, C. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4976 · Cited by 585 · see citing works
Defective platelet activation in Gαq-deficient mice
Offermanns, S., Toombs, C. F., Hu, Y.-H., & Simon, M. I. (1997) · Nature · doi:10.1038/38284 · Cited by 561 · see citing works
Nagata, K., Ohashi, K., Nakano, T., Arita, H., Zong, C., Hanafusa, H., & Mizuno, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30022 · Cited by 541 · see citing works
Tyro-3 family receptors are essential regulators of mammalian spermatogenesis
Lu, Q., Gore, M., Zhang, Q., Camenisch, T., Boast, S., Casagranda, F., Lai, C., Skinner, M. K., Klein, R., Matsushima, G. K., et al. (1999) · Nature · doi:10.1038/19554 · Cited by 514 · see citing works
Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W. C., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., et al. (1995) · Nature · doi:10.1038/373623a0 · Cited by 482 · see citing works
Léon, C., Hechler, B., Freund, M., Eckly, A. E., Vial, C., Ohlmann, P., Dierich, A., LeMeur, M., Cazenave, J., & Gachet, C. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8399 · Cited by 459 · see citing works
Fabre, J., Nguyen, M., Latour, A. M., Keifer, J. A., Audoly, L., Coffman, T. M., & Koller, B. H. (1999) · Nature Medicine · doi:10.1038/13522 · Cited by 439 · see citing works
Dahlbäck, B. (1991) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1646373 · Cited by 358 · see citing works
Self-citationCarmeliet, P., Kieckens, L., Schoonjans, L., Neugeboren, B. I., Nuffelen, A. V., Prendergast, G. C., Cole, M. D., Bronson, R. T., Collen, D., & Mulligan, R. C. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116892 · Cited by 345 · see citing works
Self-citationCloning and mRNA expression analysis of a novel human protooncogene, c-mer.
Graham, D. K., Dawson, T. L., Mullaney, D. L., Snodgrass, H. R., & Earp, H. S. (1994) · PubMed · Cited by 302 · see citing works
Cell Adhesion to Phosphatidylserine Mediated by a Product of Growth Arrest-specific Gene 6*
Nakano, T., Ishimoto, Y., Kishino, J., Umeda, M., Inoue, K., Nagata, K., Ohashi, K., Mizuno, K., & Arita, H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.47.29411 · Cited by 264 · see citing works
Goruppi, S., Ruaro, E. M., & Schneider, C. (1996) · PubMed · Cited by 262 · see citing works
Lupu, F., Bergonzelli, G. E., Heim, D. A., Cousin, E., Genton, C., Bachmann, F., & Kruithof, E. K. O. (1993) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.13.7.1090 · Cited by 257 · see citing works
Self-citationBleeding time in laboratory animals. II - A comparison of different assay conditions in rats.
Dejana, E., Callioni, A., Quintana, A., & de Gaetano, G. (1979) · Thrombosis Research · doi:10.1016/0049-3848(79)90064-1 · Cited by 222 · see citing works
Godowski, P. J., Mark, M. R., Chen, J., Sadick, M. D., Raab, H. E., & Hammonds, R. G. (1995) · Cell · doi:10.1016/0092-8674(95)90424-7 · Cited by 212 · see citing works
Chen, J., Carey, K. D., & Godowski, P. J. (1997) · Oncogene · doi:10.1038/sj.onc.1201039 · Cited by 209 · see citing works
Mark, M. R., Chen, J., Hammonds, R. G., Sadick, M. D., & Godowsk, P. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.16.9785 · Cited by 207 · see citing works
DiMinno, G., & Silver, M. J. (1983) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)33551-2 · Cited by 199 · see citing works
Role of P2Y1 purinoceptor in ADP‐induced platelet activation
Savi, P., Beauverger, P., Labouret, C., Delfaud, M., Salel, V., Kaghad, M., & Herbert, J. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00025-8 · Cited by 197 · see citing works
Self-citationGAS6 Induces Axl-mediated Chemotaxis of Vascular Smooth Muscle Cells
Fridell, Y.-W. C., Villa, J., Attar, E. C., & Liu, E. T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.12.7123 · Cited by 195 · see citing works
Identification of Gas6 as a growth factor for human Schwann cells
Li, R. Q., Chen, J., Hammonds, R. G., PHILLIPS, H. S., Armanini, M. P., Wood, P. M., Bunge, R. P., Godowski, P. J., Sliwkowski, M. X., & Mather, J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-06-02012.1996 · Cited by 190 · see citing works
Nakano, T., Higashino, K., Kikuchi, N., Kishino, J., Nomura, K., Fujita, H. M., Ohara, O., & Arita, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.11.5702 · Cited by 182 · see citing works
Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis
Neubauer, A., Fiebeler, A., Graham, D. K., O’Bryan, J. P., Schmidt, C., Barckow, P., Serke, S., Siegert, W., Snodgrass, H. R., & Huhn, D. (1994) · Blood · doi:10.1182/blood.v84.6.1931.1931 · Cited by 176 · see citing works
GAS6 Mediates Adhesion of Cells Expressing the Receptor Tyrosine Kinase Axl
McCloskey, P., Fridell, Y.-W. C., Attar, E. C., Villa, J., Jin, Y., Varnum, B. C., & Liu, E. T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23285 · Cited by 133 · see citing works
Expression of Receptor Tyrosine Kinase Axl and its Ligand Gas6 in Rheumatoid Arthritis
O’Donnell, K., Harkes, I. C., Dougherty, L., & Wicks, I. P. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65369-2 · Cited by 131 · see citing works
Importance of platelets in experimental venous thrombosis in the rat
Herbert, J., Bernat, A., & Maffrand, J. (1992) · Blood · doi:10.1182/blood.v80.9.2281.bloodjournal8092281 · Cited by 106 · see citing works
Self-citationRoth, J. (1989) · Methods in cell biology · doi:10.1016/s0091-679x(08)61625-8 · Cited by 103 · see citing works
Comparison of two experimental thrombosis models in rats effects of four glycosaminoglycans
Vogel, G. M. T., Meuleman, D. G., Bourgondiën, F. G. M., & Hobbelen, P. M. J. (1989) · Thrombosis Research · doi:10.1016/0049-3848(89)90210-7 · Cited by 92 · see citing works
A New Animal Model of Thrombophilia Confirms that High Plasma Factor VIII Levels Are Thrombogenic
Kawasaki, T., Kaida, T., Arnout, J., Vermylen, J., & Hoylaerts, M. (1999) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614471 · Cited by 82 · see citing works
Self-citationBorgel, D., Gandrille, S., & Aiach, M. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657551 · Cited by 71 · see citing works
Avanzi, G. C., Gallicchio, M., Cavalloni, G., Gammaitoni, L., Leone, F., Rosina, A., Boldorini, R. L., Monga, G., Pegoraro, L., Varnum, B. C., et al. (1997) · PubMed · Cited by 65 · see citing works
Gabbeta, J., Xu, Y., Sun, L., McLane, M. A., Niewiarowski, S., & Rao, A. K. (1996) · Blood · doi:10.1182/blood.v87.4.1368.bloodjournal8741368 · Cited by 63 · see citing works
New insights into the control of cell growth; the role of the Axl family
Crosier, K. E., & Crosier, P. S. (1997) · Pathology · doi:10.1080/00313029700169744 · Cited by 56 · see citing works
Release of a product of growth arrest‐specific gene 6 from rat platelets
Ishimoto, Y., & Nakano, T. (2000) · FEBS Letters · doi:10.1016/s0014-5793(99)01795-0 · Cited by 34 · see citing works
Evenäs, P., de Frutos, P. G., Nicolaes, G. A. F., & Dahlbäck, B. (2000) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614007 · Cited by 33 · see citing works
Self-citationStassen, J. M., Vanlinthout, I., LIJNEN, H. R., & Collen, D. (1990) · Fibrinolysis and Proteolysis · doi:10.1016/0268-9499(90)90349-o · Cited by 33 · see citing works
Self-citationMatsuno, H., Uematsu, T., Umemura, K., Takiguchi, Y., Wada, K., & Nakashima, M. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb14370.x · Cited by 29 · see citing works
Congenital Disorders of Platelet Signal Transduction
Rao, A. K., & Gabbeta, J. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.2.285 · Cited by 29 · see citing works
Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties
Grinnell, B. W., Walls, J., Marks, C., Glasebrook, A., Berg, D., Yan, S., & Bang, N. U. (1990) · Blood · doi:10.1182/blood.v76.12.2546.2546 · Cited by 28 · see citing works
Integrin Structure and Function in Hemostasis and Thrombosis
BENNETT, J. S. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb43704.x · Cited by 17 · see citing works
Umemura, K., Nishiyama, H., Kikuchi, S., Kondo, K., & Nakashima, M. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650663 · Cited by 12 · see citing works
Prediction of IgE(Lb4)–ligand complex structures by automated docking
Winger, R. H., Liedl, K. R., Sotriffer, C., Gamper, A. M., Rode, B. M., Kroemer, R. T., & Varga, J. M. (1996) · Journal of Molecular Recognition · doi:10.1002/(sici)1099-1352(199605)9:3 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Yan, S.B. Review of conformation-specific affinity purification methods for plasma vitamin K-dependent proteins. J. Mol. Recognit. 9, 211-218 (1996).
Cited by
Sorted by citations
Mechanisms of Thrombus Formation
Furie, B., & Furie, B. C. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801082 · Cited by 1,926 · see citing works
Thrombosis as an intravascular effector of innate immunity
Engelmann, B., & Massberg, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3345 · Cited by 1,989 · see citing works
von Brühl, M.-L., Stark, K., Steinhart, A., Chandraratne, S., Konrad, I., Lorenz, M., Khandoga, A. G., Tirniceriu, A., Coletti, R., Köllnberger, M., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112322 · Cited by 1,827 · see citing works
“…restriction in mice induces venous thrombosis resembling human DVT Most of our current mechanistic knowledge regarding DVT pathophysiology has been gained from mouse models using denudation of the venous endothelial surface (Eitzman et al., 2000; Angelillo-Scherrer et al., 2001; Wang et al., 2006).”
BackgroundInfluentialRankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340 · see citing works
TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response
Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., & Lemke, G. (2007) · Cell · doi:10.1016/j.cell.2007.10.034 · Cited by 1,055 · see citing works
“Mouse knockouts have also been reported for Gas6 (Angelillo-Scherrer et al., 2001), and it will be of interest to examine circulating levels of inflammatory cytokines in these mutants.”
BackgroundPhagocytosis of apoptotic cells in homeostasis
Arandjelovic, S., & Ravichandran, K. S. (2015) · Nature Immunology · doi:10.1038/ni.3253 · Cited by 959 · see citing works
Autoimmunity and the Clearance of Dead Cells
Nagata, S., Hanayama, R., & Kawane, K. (2010) · Cell · doi:10.1016/j.cell.2010.02.014 · Cited by 877 · see citing works
Immunobiology of the TAM receptors
Lemke, G., & Rothlin, C. V. (2008) · Nature reviews. Immunology · doi:10.1038/nri2303 · Cited by 867 · see citing works
Coppinger, J. A., Cagney, G., Toomey, S., Kislinger, T., Belton, O., McRedmond, J. P., Cahill, D. J., Emili, A., Fitzgerald, D. J., & Maguire, P. B. (2003) · Blood · doi:10.1182/blood-2003-08-2804 · Cited by 813 · see citing works
An Apoptotic ‘Eat Me’ Signal: Phosphatidylserine Exposure
Segawa, K., & Nagata, S. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.08.003 · Cited by 778 · see citing works
“Gas6 and protein S are important for blood clotting; a deficiency in either protein causes platelet dysfunction [54,55], suggesting that their roles are not redundant.”
BackgroundAdhesion Mechanisms in Platelet Function
Ruggeri, Z. M., & Mendolicchio, G. L. (2007) · Circulation Research · doi:10.1161/01.res.0000267878.97021.ab · Cited by 759 · see citing works
Linger, R. M. A., Keating, A. K., Earp, H. S., & Graham, D. K. (2008) · Advances in cancer research · doi:10.1016/s0065-230x(08)00002-x · Cited by 750 · see citing works
“Within the hematopoietic lineages, Mer is expressed in monocytes/ macrophages, dendritic cells, NK cells, NKT cells, megakaryocytes, and platelets (Angelillo‐Scherrer et al., 2001; Behrens et al., 2003; Graham et al., 1994).”
BackgroundThe growing complexity of platelet aggregation
Jackson, S. P. (2007) · Blood · doi:10.1182/blood-2006-12-027698 · Cited by 741 · see citing works
The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer
Graham, D. K., DeRyckere, D., Davies, K. D., & Earp, H. S. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3847 · Cited by 708 · see citing works
Arterial thrombosis—insidious, unpredictable and deadly
Jackson, S. P. (2011) · Nature Medicine · doi:10.1038/nm.2515 · Cited by 686 · see citing works
Defective thrombus formation in mice lacking coagulation factor XII
Renné, T., Požgajová, M., Grüner, S., Schuh, K., Pauer, H., Burfeind, P., Gailani, D., & Nieswandt, B. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050664 · Cited by 684 · see citing works
“However, fibronectin-deficient mice do not form occlusive arterial thrombi, and Gas6null mice are protected from thromboembolism (33, 34).”
BackgroundTAM receptors regulate multiple features of microglial physiology
Fourgeaud, L., Través, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagórska, A., Rothlin, C. V., Nimmerjahn, A., et al. (2016) · Nature · doi:10.1038/nature17630 · Cited by 600 · see citing works
Lemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598 · see citing works
Integrins: dynamic scaffolds for adhesion and signaling in platelets
Shattil, S. J., & Newman, P. J. (2004) · Blood · doi:10.1182/blood-2004-04-1257 · Cited by 600 · see citing works
The Hemostatic System as a Modulator of Atherosclerosis
Borissoff, J. I., Spronk, H. M. H., & Cate, H. T. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011670 · Cited by 566 · see citing works
Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells
Bosurgi, L., Cao, Y. G., Cabeza-Cabrerizo, M., Tucci, A., Hughes, L. D., Kong, Y., Weinstein, J. S., Licona-Limon, P., Schmid, E. T., Pelorosso, F., et al. (2017) · Science · doi:10.1126/science.aai8132 · Cited by 560 · see citing works
TAM Receptor Signaling in Immune Homeostasis
Rothlin, C. V., Silva, E. A. C., Bosurgi, L., & Ghosh, S. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112103 · Cited by 516 · see citing works
“Angelillo-Scherrer and colleagues (96, 97) were the first to ascribe this phenotype to the function of TAM RTKs and GAS6 in the stabilization of thrombus formation (Figure 3).”
BackgroundPlatelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype
Podrez, E. A., Byzova, T. V., Febbraio, M., Salomon, R. G., Ma, Y., Valiyaveettil, M., Poliakov, E., Sun, M., Finton, P. J., Curtis, B. R., et al. (2007) · Nature Medicine · doi:10.1038/nm1626 · Cited by 513 · see citing works
Platelets: Physiology and Biochemistry
Jurk, K., & Kehrel, B. E. (2005) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-2005-916671 · Cited by 512 · see citing works
Platelets at work in primary hemostasis
Broos, K., Feys, H. B., Meyer, S. F. D., Vanhoorelbeke, K., & Deckmyn, H. (2011) · Blood Reviews · doi:10.1016/j.blre.2011.03.002 · Cited by 501 · see citing works
Zhu, C., Wei, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1090-3 · Cited by 498 · see citing works
Furie, B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26987 · Cited by 486 · see citing works
Diversification of TAM receptor tyrosine kinase function
Zagórska, A., Través, P. G., Lew, E. D., Dransfield, I., & Lemke, G. (2014) · Nature Immunology · doi:10.1038/ni.2986 · Cited by 430 · see citing works
Platelet receptors and signaling in the dynamics of thrombus formation
Rivera, J., Lozano, M. L., Navarro‐Núñez, L., & Vicente, V. (2009) · Haematologica · doi:10.3324/haematol.2008.003178 · Cited by 416 · see citing works
“axis in thrombus formation and vascular wall homeostasis.(93,94) Biochemical studies have shown that Gas-6 mediated signaling reinforces αIIbβ3 outside-in signaling by activation of PI3-K and Akt, and promotes β3 phosphorylation and therefore clot retraction.”
BackgroundScientific and therapeutic advances in antiplatelet therapy
Bhatt, D. L., & Topol, E. J. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd985 · Cited by 409 · see citing works
Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets
Müller, I., Klocke, A., Alex, M., Kotzsch, M., Luther, T., Morgenstern, E., Zieseniss, S., Stefan Zahler, A., Preissner, K., & Engelmann, B. (2003) · The FASEB Journal · doi:10.1096/fj.02-0574fje · Cited by 401 · see citing works
“Furthermore, mice deficient in the platelet secretion product Gas6 (31) are also resistant to the formation of venous thrombemboli in response to collagen.”
BackgroundKonstantinides, S., Schäfer, K., Koschnick, S., & Loskutoff, D. J. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13143 · Cited by 373 · see citing works
“Finally, it is interesting to note that inactivation of the Gas 6 gene in mice also protected them from injury-induced thrombosis (36).”
BackgroundPlatelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke
Nieswandt, B., Pleines, I., & Bender, M. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04361.x · Cited by 358 · see citing works
André, P., Delaney, S. M., LaRocca, T., Vincent, D., DeGuzman, F. R., Jurek, M., Koller, B., Phillips, D. R., & Conley, P. B. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17864 · Cited by 358 · see citing works
“As platelets release thrombogenic mediators such as CD40L and Gas6 upon activation (28, 29), this could further reduce the thrombogenicity of a P2Y12 growing thrombus.”
BackgroundHafizi, S., & Dahlbäck, B. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05529.x · Cited by 356 · see citing works
Self-citationTAM receptors, Gas6, and protein S: roles in inflammation and hemostasis
van der Meer, J. H. M., van der Poll, T., & Veer, C. V. ′. (2014) · Blood · doi:10.1182/blood-2013-09-528752 · Cited by 341 · see citing works
Sather, S., Kenyon, K. D., Lefkowitz, J. B., Liang, X., Varnum, B. C., Henson, P. M., & Graham, D. K. (2006) · Blood · doi:10.1182/blood-2006-05-021634 · Cited by 333 · see citing works
The clearance of dying cells: table for two
Green, D. R., Oguin, T. H., & Martinez, J. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.172 · Cited by 314 · see citing works
Structural basis for Gas6–Axl signalling
Sasaki, T., Knyazev, P. G., Clout, N. J., Cheburkin, Y. V., Göhring, W., Ullrich, A., Timpl, R., & Hohenester, E. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600912 · Cited by 304 · see citing works
“Recent gene knockout studies have revealed fundamental roles of Axl RTKs in spermatogenesis (Lu et al, 1999), immunity (Lu and Lemke, 2001; Scott et al, 2001), platelet function (Angelillo-Scherrer et al, 2001, 2005) and kidney pathology (Yanagita et al, 2002).”
BackgroundLi, Y., Ye, X., Tan, C., Hongo, J. A., Zha, J., Liu, J., Kallop, D. Y., Ludlam, M. J. C., & Pei, L. (2009) · Oncogene · doi:10.1038/onc.2009.212 · Cited by 289 · see citing works
Integration of Proteomics and Genomics in Platelets
McRedmond, J. P., Park, S. D., Reilly, D. F., Coppinger, J. A., Maguire, P. B., Shields, D. C., & Fitzgerald, D. J. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m300063-mcp200 · Cited by 285 · see citing works
Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities
Lew, E. D., Oh, J., Burrola, P., Lax, I., Zagórska, A., Través, P. G., Schlessinger, J., & Lemke, G. (2014) · eLife · doi:10.7554/elife.03385 · Cited by 271 · see citing works
“The Tyro3−/−, Axl−/−, and Mertk−/− mutants (Lu et al., 1999), the Gas6−/− mutants (Angelillo-Scherrer et al., 2001), and the floxed Pros1 mutants (Burstyn-Cohen et al., 2012) were all as described previously.”
Backgroundvon Hundelshausen, P., & Lievens, D. (2011) · Thrombosis and Haemostasis · doi:10.1160/th11-08-0592 · Cited by 268 · see citing works
“During platelet activation, both growth-arrest-specific gene 6 (GAS6) and CD40 ligand (CD40L) are present in the platelet-platelet synapse and enhance stabilisation (31, 32).”
BackgroundTAM receptor function in the retinal pigment epithelium
Prasad, D., Rothlin, C. V., Burrola, P., Burstyn-Cohen, T., Lu, Q., Garcia de Frutos, P., & Lemke, G. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.06.011 · Cited by 270 · see citing works
“, 1999), whereas Gas6 mutant males are fertile (Angelillo-Scherrer et al., 2001).”
BackgroundResultInfluentialAngelillo‐Scherrer, A., Burnier, L., Flores, N., Savi, P., DeMol, M., Schaeffer, P., Herbert, J., Lemke, G., Goff, S. P., Matsushima, G. K., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22079 · Cited by 269 · see citing works
“Platelets from WT mice dose-dependently aggregated in response to increasing concentrations of ADP, collagen, or the TXA2 analogue U46619, achieving a maximal effect at concentrations similar to those previously reported (7).”
BackgroundInfluentialSelf-citationRuggeri, Z. M. (2009) · Microcirculation · doi:10.1080/10739680802651477 · Cited by 254 · see citing works
“Growth arrest specific gene 6 product (Gas6) is a vitamin K dependent protein homologous to the anticoagulant cofactor, protein S, whose absence or inactivation was reported to protect mice from fatal thromboembolism [7].”
BackgroundTAM receptors and the clearance of apoptotic cells
Lemke, G., & Burstyn‐Cohen, T. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05744.x · Cited by 244 · see citing works
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A. J., Musser, M., Yuan, J., Wei, K., Kuo, C. J., Longacre, T. A., & Giaccia, A. J. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1267 · Cited by 229 · see citing works
Targeting Axl and Mer Kinases in Cancer
Verma, A. R., Warner, S. L., Vankayalapati, H., Bearss, D. J., & Sharma, S. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0116 · Cited by 226 · see citing works
“lineages such asmonocytes, macrophages, dendritic cells, natural killer (NK) cells, megakaryocytes, and platelets (3, 4).”
BackgroundVitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?
McCann, J. C., & Ames, B. N. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27930 · Cited by 221 · see citing works
“In contrast, other responses suggest the opposite [eg, decreased thrombus formation in a prothrombotic model (70, 145), less nephrotoxic nephritis in a disease model (156), and decreased inflammation in an induced atherosclerosis model (124)].”
Batalla, I. B., Schultze, A., Wroblewski, M., Erdmann, R., Heuser, M., Waizenegger, J. S., Riecken, K., Binder, M., Schewe, D. M., Sawall, S., et al. (2013) · Blood · doi:10.1182/blood-2013-03-491431 · Cited by 218 · see citing works
Self-citationMacrophages Regulate Schwann Cell Maturation after Nerve Injury
Stratton, J. A., Holmes, A. L., Rosin, N. L., Sinha, S., Vohra, M., Burma, N. E., Trang, T., Midha, R., & Biernaskie, J. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.004 · Cited by 213 · see citing works
Prasad, K. S. S., André, P., He, M.-S., Bao, M., Manganello, J. M., & Phillips, D. R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2032886100 · Cited by 207 · see citing works
TAM receptor signaling and autoimmune disease
Rothlin, C. V., & Lemke, G. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.10.001 · Cited by 198 · see citing works
TNF-α, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages
Alciato, F., Sainaghi, P. P., Sola, D., Castello, L. M., & Avanzi, G. C. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0909610 · Cited by 194 · see citing works
“Interaction of GAS6 with its receptors has been evaluated in several biological systems such as platelet aggregation [9, 10], angiogenesis [11], and cell growth/survival [12].”
BackgroundAntiplatelet therapy: in search of the 'magic bullet'
Jackson, S. P., & Schoenwaelder, S. M. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1198 · Cited by 195 · see citing works
AXL kinase as a novel target for cancer therapy
Wu, X., Liu, X., Koul, S., Lee, C. Y., Zhang, Z., & Halmos, B. (2014) · Oncotarget · doi:10.18632/oncotarget.2542 · Cited by 191 · see citing works
“com/oncotarget [8–10].”
BackgroundPhosphatidylserine receptors: Enhancers of enveloped virus entry and infection
Møller-Tank, S., & Maury, W. J. (2014) · Virology · doi:10.1016/j.virol.2014.09.009 · Cited by 186 · see citing works
“Platelets (Angelillo-Scherrer et al., 2001) Rhabdovirus: New World Arenavirus:”
Murine Models of Vascular Thrombosis
Westrick, R. J., Winn, M. E., & Eitzman, D. T. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.142810 · Cited by 184 · see citing works
The physiology of vitamin K nutriture and vitamin K‐dependent protein function in atherosclerosis
Berkner, K. L., & Runge, K. W. (2004) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2004.00968.x · Cited by 184 · see citing works
Vascular calcification: The price to pay for anticoagulation therapy with vitamin K-antagonists
Chatrou, M. L. L., Winckers, K., Hackeng, T. M., Reutelingsperger, C. P. M., & Schurgers, L. J. (2012) · Blood Reviews · doi:10.1016/j.blre.2012.03.002 · Cited by 177 · see citing works
Lack of Protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis
Burstyn‐Cohen, T., Heeb, M. J., & Lemke, G. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39325 · Cited by 177 · see citing works
Furie, B., & FURIE, B. C. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02482.x · Cited by 172 · see citing works
Ghosh, A., Li, W., Febbraio, M., Espinola, R. G., McCrae, K. R., Cockrell, E., & Silverstein, R. L. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34904 · Cited by 169 · see citing works
“These include ephrins and their receptors, eph kinases (50, 51); gas6 and its tyrosine kinase receptors, mer, tyro3, and axl (52, 53); PECAM-1 (54); CD40 and CD40L (55, 56); and semaphorin 4D (57).”
BackgroundThe Receptor Tyrosine Kinase AXL in Cancer Progression
Rankin, E. B., & Giaccia, A. J. (2016) · Cancers · doi:10.3390/cancers8110103 · Cited by 170 · see citing works
“Moreover, analysis of Axl and Gas6 germline knockout mice shows that the GAS6/AXL signaling cascade is not required for embryonic development or normal tissue function indicating that specific GAS6/AXL inhibitors may not be associated with normal tissue toxicities [9,10].”
BackgroundBurstyn-Cohen, T., Lew, E. D., Través, P. G., Burrola, P. G., Hash, J. C., & Lemke, G. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.015 · Cited by 163 · see citing works
“…/ , Axl / , and Mertk / mutants (Lu et al., 1999), the Pros1fl/fl conditional and Pros1 / mutants (Burstyn-Cohen et al., 2009), the Gas6 / mutants (Angelillo-Scherrer et al., 2001), the Trp1-Cre driver line (Mori et al., 2002), and the Nestin-Cre driver line (Tronche et al., 1999) have all been…”
InfluentialMalignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6
Loges, S., Schmidt, T., Tjwa, M., Geyte, K. V., Lievens, D., Lutgens, E., Vanhoutte, D., Borgel, D., Plaisance, S., Hoylaerts, M., et al. (2009) · Blood · doi:10.1182/blood-2009-06-228684 · Cited by 163 · see citing works
Self-citationTjwa, M., Bellido‐Martín, L., Lin, Y., Lutgens, E., Plaisance, S., Bono, F., Delesque-Touchard, N., Hervé, C., Moura, R., Billiau, A., et al. (2007) · Blood · doi:10.1182/blood-2007-05-089565 · Cited by 162 · see citing works
Self-citationADP and platelets: the end of the beginning
Woulfe, D. S., Yang, J., & Brass, L. F. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13361 · Cited by 158 · see citing works
In Vivo Thrombus Formation in Murine Models
Sachs, U. J., & Nieswandt, B. (2007) · Circulation Research · doi:10.1161/01.res.0000261936.85776.5f · Cited by 158 · see citing works
Akalu, Y. T., Rothlin, C. V., & Ghosh, S. (2017) · Immunological Reviews · doi:10.1111/imr.12522 · Cited by 156 · see citing works
Atherosclerotic Plaque Rupture
Lutgens, E., van Suylen, R. J., Faber, B. C. G., Gijbels, M. J., Eurlings, P. M. H., Bijnens, A. P., Cleutjens, K. B. J. M., Heeneman, S., & Daemen, M. J. A. P. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000097783.01596.e2 · Cited by 154 · see citing works
Prévost, N., Woulfe, D. S., Jiang, H., Stalker, T. J., Marchese, P., Ruggeri, Z. M., & Brass, L. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404065102 · Cited by 153 · see citing works
Gustafsson, A., Martuszewska, D., Johansson, M., Ekman, C., Hafizi, S., Ljungberg, B., & Dahlbäck, B. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2514 · Cited by 152 · see citing works
Self-citationThe receptor tyrosine kinase Axl in cancer: Biological functions and therapeutic implications
Paccez, J. D., Vogelsang, M., Parker, M. I., & Zerbini, L. F. (2013) · International Journal of Cancer · doi:10.1002/ijc.28246 · Cited by 148 · see citing works
Coordinate regulation of neutrophil homeostasis by liver X receptors in mice
Hong, C., Kidani, Y., A-González, N., Phung, T., Ito, A., Rong, X., Ericson, K. R., Mikkola, H. K. A., Beaven, S. W., Miller, L. S., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58393 · Cited by 152 · see citing works
Future innovations in anti‐platelet therapies
Barrett, N. E., Holbrook, L., Jones, S., Kaiser, W. J., Moraes, L. A., Rana, R., Sage, T., STANLEY, R. G., Tucker, K. L., Wright, B., et al. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.151 · Cited by 151 · see citing works
“Abnormal to thrombin—loosely packed aggregates, incomplete degranulation Unchanged bleeding time Angelillo-Scherrer et al., 2001 Plasma fibronectin Widely expressed No change in adhesion.”
BackgroundInfluentialHall, M. O., Obin, M. S., Heeb, M. J., Burgess, B. L., & Abrams, T. A. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.03.017 · Cited by 145 · see citing works
Efferocytosis in the tumor microenvironment
Werfel, T. A., & Cook, R. S. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-018-0698-5 · Cited by 156 · see citing works
Nanda, N., Bao, M., Lin, H., Clauser, K. R., Kömüves, L. G., Quertermous, T., Conley, P. B., Phillips, D. R., & Hart, M. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413411200 · Cited by 145 · see citing works
Keating, A. K., Kim, G. K., Jones, A. E., Donson, A. M., Ware, K. E., Mulcahy, J. M., Salzberg, D. B., Foreman, N. K., Liang, X., Thorburn, A. M., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0707 · Cited by 143 · see citing works
“org any single receptor yields the phenotype of diminished platelet aggregation and clot stability (25, 26).”
An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis
Kariolis, M. S., Miao, Y. R., Jones, D. S., Kapur, S., Mathews, I. I., Giaccia, A. J., & Cochran, J. R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1636 · Cited by 143 · see citing works
Washington, A. V., Gibot, S., Acevedo, I., Gattis, J., Quigley, L., Feltz, R., Mota, A. D. L., Schubert, R. L., Gómez‐Rodríguez, J., Cheng, J., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36175 · Cited by 142 · see citing works
Minding the gaps to promote thrombus growth and stability
Brass, L. F. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26869 · Cited by 140 · see citing works
Binder, M. D., Cate, H. S., Prieto, A. L., Kemper, D., Butzkueven, H., Gresle, M. M., Cipriani, T., Jokubaitis, V. G., Carmeliet, P., & Kilpatrick, T. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1180-08.2008 · Cited by 138 · see citing works
“Demyelination is increased in Gas6 / mice We next examined the effect of administering cuprizone to mice lacking expression of Gas6 (Angelillo-Scherrer et al., 2001).”
BackgroundSelf-citationPlatelet response heterogeneity in thrombus formation
Auger, J. M., Munnix, I. C. A., Cosemans, J. M. E. M., & Heemskerk, J. W. M. (2009) · Thrombosis and Haemostasis · doi:10.1160/th09-05-0289 · Cited by 137 · see citing works
“Next to ADP and TxA2, several other soluble release products are described with a proaggregatory effect, such as ATP, Gas6, serotonin and cytokines (4, 22, 23).”
BackgroundGynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles
Razavi, Z. S., Tajiknia, V., Majidi, S., Ghandali, M., Mirzaei, H. R., Rahimian, N., Hamblin, M. R., & Mirzaei, H. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.103192 · Cited by 132 · see citing works
Prévost, N., Woulfe, D. S., Tanaka, T. I., & Brass, L. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142053899 · Cited by 130 · see citing works
Intracellular signaling pathways involved in Gas6-Axl-mediated survival of endothelial cells
Hasanbasic, I., Cuerquis, J., Varnum, B., & Blostein, M. D. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00020.2004 · Cited by 156 · see citing works
“Finally, homozygous null Gas6 mice have a platelet dysfunction that protect mice against lethal intravascular thrombosis (1).”
BackgroundAnalysis of Gas6 in Human Platelets and Plasma
Balogh, I., Hafizi, S., Stenhoff, J., Hansson, K., & Dahlbäck, B. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000163845.07146.48 · Cited by 125 · see citing works
“18 As the concentration of Gas6 in plasma is very low, it is unlikely that plasma contamination of the platelet preparation used could explain the reported presence of Gas6 in platelets in the previous study.(18) Gas6 is capable of binding to different cell surfaces via its N- and C-termini, the N-terminal Gla domain…”
Self-citationVitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac fibroblasts
Stenhoff, J., Dahlbäck, B., & Hafizi, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.070 · Cited by 124 · see citing works
Self-citationPlatelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis
Denis, C. V., & Wagner, D. D. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000259359.52265.62 · Cited by 123 · see citing works
Suleiman, L., Négrier, C., & Boukerche, H. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.07.004 · Cited by 120 · see citing works
“[61] Angelillo-Scherrer A, de Frutos P, Aparicio C, et al.”
BackgroundInfluentialGas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses
Gould, W. R., Baxi, S. M., SCHROEDER, R., Peng, Y., Leadley, R. J., Peterson, J. T., & Perrin, L. A. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01186.x · Cited by 119 · see citing works
Axl, A Receptor Tyrosine Kinase, Mediates Flow-Induced Vascular Remodeling
Korshunov, V. A., Mohan, A. M., Georger, M. A., & Berk, B. C. (2006) · Circulation Research · doi:10.1161/01.res.0000223322.16149.9a · Cited by 116 · see citing works
Sawabu, T., Seno, H., Kawashima, T., Fukuda, A., Uenoyama, Y., Kawada, M., Kanda, N., Sekikawa, A. M., Fukui, H., Yanagita, M., et al. (2006) · Molecular Carcinogenesis · doi:10.1002/mc.20211 · Cited by 112 · see citing works
Day, S. M., Reeve, J., Myers, D. D., & Fay, W. P. (2004) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613739 · Cited by 112 · see citing works
“5 mg/kg), usually via the jugular vein (13, 16).”
BackgroundGallicchio, M., Mitola, S. M. F., Valdembri, D., Fantozzi, R., Varnum, B. C., Avanzi, G. C., & Bussolino, F. (2004) · Blood · doi:10.1182/blood-2004-04-1469 · Cited by 112 · see citing works
Gas6 Anti-apoptotic Signaling Requires NF-κB Activation
Demarchi, F., Verardo, R., Varnum, B. C., Brancolini, C., & Schneider, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104457200 · Cited by 108 · see citing works
Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kα pathway
Hers, I. (2007) · Blood · doi:10.1182/blood-2006-10-050633 · Cited by 109 · see citing works
“I demonstrate that IGF-1 stimulates (1) rapid and dose-dependent tyrosine phosphorylation of the subunit of the IGF receptor, (2) transient tyrosine phosphorylation of IRS-1 and IRS-2, (3) association of IRS-1 and IRS-2 with the SH2-containing p85 subunit of PI3K, and (4) transient phosphorylation of PKB on Ser473.”
Background
- Authors
- Angelillo-Scherrer, A., de Frutos, P. G., Aparicio, C., Melis, E., Savi, P., Lupu, F., Arnout, J., Dewerchin, M., Hoylaerts, M. F., Herbert, J.-M., Collen, D., Dahlbäck, B., & Carmeliet, P.
- Affiliations
- Lund University (SE)
- Sanofi (France) (FR)
- Thrombosis Research Institute (GB)
- Corresponding author
- Carmeliet, Peter
- Venue
- Nature Medicine
- Published
- 2001-02
- Volume
- 7
- Issue
- 2
- Pages
- 215-221
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2137108685
- Cited by
- 441
- References
- 44
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 8 · 2020: 16 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 26 · 2015: 26 · 2014: 21 · 2013: 14 · 2012: 22
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Sanofi
- Stiftelsen för Strategisk Forskning
- Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- Gas6, thrombosis, platelet dysfunction, platelet aggregation, hemostasis, thromboembolism, platelet secretion, thromboprophylaxis
- MeSH terms
- Growth Arrest-Specific Protein 6, Animals, Blood Platelets, Cell Line, Disease Models, Animal, Female, Hemostasis, Humans, Male, Phenotype, Platelet Aggregation, Proteins, Receptors, Cell Surface, Recombinant Proteins, Thrombosis, Gene Expression, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Mice
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