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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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“Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice”
From Hypoxic control of metastasis (2016) · cites this paper as [88]
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Citations
Cites
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
Dahlbäck, B. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02225-x · Cited by 613
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
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
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
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
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
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
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
Dahlbäck, B. (1991) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1646373 · Cited by 349
Self-citation
Cited by
Sorted by citations
Items 101–200 of 442
Cosemans, J. M. E. M., van Kruchten, R., Olieslagers, S., Schurgers, L. J., Verheyen, F., Munnix, I. C. A., Waltenberger, J. L., Angelillo‐Scherrer, A., Hoylaerts, M., Carmeliet, P., et al. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03935.x · Cited by 108
Self-citationGas6 is complexed to the soluble tyrosine kinase receptor Axl in human blood
Ekman, C. J., Stenhoff, J., & Dahlbäck, B. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03752.x · Cited by 108
Self-citationPlatelet aggregation induces platelet aggregate stability via SLAM family receptor signaling
Nanda, N., André, P., Bao, M., Clauser, K. R., DeGuzman, F. R., Howie, D., Conley, P. B., Terhorst, C., & Phillips, D. R. (2005) · Blood · doi:10.1182/blood-2005-01-0333 · Cited by 107
Nagai, K., Arai, H., Yanagita, M., Matsubara, T., Kanamori, H., Nakano, T., Iehara, N., Fukatsu, A., Kita, T., & Doi, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213266200 · Cited by 106
Activation of TYRO3/AXL Tyrosine Kinase Receptors in Thyroid Cancer
Avilla, E., Guarino, V., Visciano, C., Liotti, F., Svelto, M., Krishnamoorthy, G., Franco, R., & Melillo, R. M. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2186 · Cited by 103
“migration and adhesion (9), vascular smooth muscle homeostasis (10), platelet function (11; 12), and erythropoiesis (11).”
Inhibition of Endogenous Leptin Protects Mice From Arterial and Venous Thrombosis
Konstantinides, S., Schäfer, K., Neels, J. G., Dellas, C., & Loskutoff, D. J. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000146531.79402.9a · Cited by 104
The effects of arterial flow on platelet activation, thrombus growth, and stabilization
Cosemans, J. M. E. M., Angelillo‐Scherrer, A., Mattheij, N. J. A., & Heemskerk, J. W. M. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt110 · Cited by 102
“plasma and limitedly stored in platelets) with the platelet TAM receptors, Tyro, Axl, and Mer.(51) –53 New data yet suggest that plasma Gas6”
BackgroundSelf-citationPlatelets and Anti-platelet Therapy
McNicol, A., & Israels, S. J. (2003) · Journal of Pharmacological Sciences · doi:10.1254/jphs.93.381 · Cited by 102
Long non‐coding RNA: A new paradigm for lung cancer
Khandelwal, A., Bacolla, A., Vásquez, K. M., & Jain, A. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22362 · Cited by 102
“GAS6-AS1 levels are inversely correlated with those of the GAS6 gene, whose product serves as a ligand for the Axl/Sky family of tyrosine kinases [112,113].”
BackgroundInactive Matrix Gla Protein Is Causally Related to Adverse Health Outcomes
Liu, Y.-P., Gu, Y.-M., Thijs, L., Knapen, M. H. J., Salvi, E., Citterio, L., Petit, T., Carpini, S. D., Zhang, Z., Jacobs, L., et al. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.04494 · Cited by 100
“In animal studies, Gas6 antagonism protected mice against thromboembolism and inflammation.(30,31) Thus, lack of vitamin K in the arterial wall, as reflected by high level of dp–ucMGP, decreases the levels of active Gas6 and increases protection against thrombosis and inflammation, processes that both play an importan…”
BackgroundGrowth Arrest-Specific Gene 6 (gas6) and Vascular Hemostasis
Laurance, S., Lemarié, C. A., & Blostein, M. D. (2012) · Advances in Nutrition · doi:10.3945/an.111.001826 · Cited by 103
“More recently, Cosemans et al. (73) described a synergistic effect of gas6 on the ADP pathway leading to the activation of aIIbb3 integrin.”
BackgroundInfluentialMERTK as negative regulator of human T cell activation
Cabezón, R., Silva, E. A. C., Flórez‐Grau, G., Errasti, A. E., Calderón‐Gómez, E., Lozano, J. J., a, C. E., Ricart, E., Panés, J., Rothlin, C. V., et al. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3a0714-334r · Cited by 101
“In humans, MERTK is expressed on DCs, NK cells, B cells, M2c macrophages, and platelets [16 – 18].”
BackgroundMERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system
Huelse, J. M., Fridlyand, D. M., Earp, S. H., DeRyckere, D., & Graham, D. K. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107577 · Cited by 101
Role of Gas6 in erythropoiesis and anemia in mice
Angelillo‐Scherrer, A., Burnier, L., Lambrechts, D., Fish, R. J., Tjwa, M., Plaisance, S., Sugamele, R., DeMol, M., Martínez-Soria, E., Maxwell, P. H., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci30375 · Cited by 105
Self-citationREVIEW ARTICLES: Platelet G protein-coupled receptors in hemostasis and thrombosis
Woulfe, D. S. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01338.x · Cited by 99
The role of γ-carboxylation in the anti-apoptotic function of gas6
Hasanbasic, I., Rajotte, I., & Blostein, M. D. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01662.x · Cited by 98
Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis
Borgel, D., Clauser, S., Bornstain, C., Bièche, I., Bissery, A., Remones, V., Fagon, J.-Y., Aiach, M., & Diehl, J. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000195014.56254.8a · Cited by 96
“As Gas6 may be released in vitro by platelets (8), we compared Gas6 concentrations in blood collected in the absence and presence of specific platelet inhibitors (CTAD, Becton Dickinson, Le-Pont-de-Claix, France).”
MethodA guide to murine platelet structure, function, assays, and genetic alterations
Jiroušková, M., Shet, A. S., & JOHNSON, G. J. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02407.x · Cited by 105
Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer
Tanaka, M., & Siemann, D. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189953 · Cited by 94
Growth arrest-specific gene 6 (GAS6)
Fernández-Fernández, L., Bellido‐Martín, L., & de Frutos, P. G. (2008) · Thrombosis and Haemostasis · doi:10.1160/th08-04-0253 · Cited by 97
Essential role of Gas6 for glomerular injury in nephrotoxic nephritis
Yanagita, M., Ishimoto, Y., Arai, H., Nagai, K., Ito, T., Nakano, T., Salant, D. J., Fukatsu, A., Doi, T., & Kita, T. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14861 · Cited by 93
“reported that deficiency of Gas6 protects mice from thrombosis (24).”
BackgroundLee, Y.-J., Han, J., Byun, J., Park, H.-J., Park, E., Chong, Y. H., Cho, M.-S., & Kang, J. L. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0611289 · Cited by 95
“Mer may also have other functions, in that Mer activation promotes macrophage survival in response to oxidative stress [31] and platelet aggregation [14, 47, 48].”
BackgroundCrystal Structure of a C-terminal Fragment of Growth Arrest-specific Protein Gas6
Sasaki, T., Knyazev, P. G., Cheburkin, Y. V., Göhring, W., Tisi, D., Ullrich, A., Timpl, R., & Hohenester, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207340200 · Cited by 91
Ekman, C. J., Jönsen, A., Sturfelt, G., Bengtsson, A. A., & Dahlbäck, B. (2011) · Rheumatology · doi:10.1093/rheumatology/keq459 · Cited by 92
Self-citationTAM Receptor Pathways at the Crossroads of Neuroinflammation and Neurodegeneration
Tondo, G., Perani, D., & Comi, C. (2019) · Disease Markers · doi:10.1155/2019/2387614 · Cited by 88
Mer Receptor Tyrosine Kinase Signaling Participates in Platelet Function
Chen, C., Li, Q., Darrow, A. L., Wang, Y., Derian, C. K., Yang, J., de Garavilla, L., Andrade‐Gordon, P., & Damiano, B. P. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000130662.30537.08 · Cited by 88
Generation and phenotypic analysis of protein S–deficient mice
Saller, F., Brisset, A. C., Tchaikovski, S. N., Azevedo, M., Chrast, R., Fernández, J. A., Schapira, M., Hackeng, T. M., Griffin, J. H., & Angelillo‐Scherrer, A. (2009) · Blood · doi:10.1182/blood-2009-03-209031 · Cited by 87
Self-citationLigand Recognition and Homophilic Interactions in Tyro3
Heiring, C., Dahlbäck, B., & Muller, Y. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311750200 · Cited by 85
Self-citationZhang, B., & Ginsburg, D. (2004) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2004.00857.x · Cited by 86
Budagian, V., Bulanova, E., Orinska, Z., Duitman, E. H., Brandt, K., Ludwig, A., Hartmann, D., Lemke, G., Säftig, P., & Bulfone‐Paus, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9324-9339.2005 · Cited by 84
“Contrary to the role of protein S as a natural anticoagulation factor, Gas6 stimulates platelets, and Gas6 / mice have a platelet aggregation defect that confers protection against thrombosis (4, 5).”
BackgroundRetractedNaik, M. U., Stalker, T. J., Brass, L. F., & Naik, U. P. (2012) · Blood · doi:10.1182/blood-2011-12-397398 · Cited by 82
Pierce, A. M., Bliesner, B., Xu, M., Nielsen‐Preiss, S. M., Lemke, G., Tobet, S. A., & Wierman, M. E. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0169 · Cited by 87
“Although initial reports suggested that Gas6-null mice are reproductively normal (39, 40), further detailed analysis of these mice will be necessary to clarify whether the effects observed in the DKO mice in this study are dependent on signaling through the Gas6 ligand.”
BackgroundTherapeutic approaches in arterial thrombosis
Phillips, D. R., Conley, P. B., Sinha, U., & André, P. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01418.x · Cited by 81
Growth Arrest–Specific Protein 6 Is Hepatoprotective Against Murine Ischemia/Reperfusion Injury
Llacuna, L., Bárcena, C., Bellido‐Martín, L., Fernández, L., Stefanović, M., Marı́, M., García‐Ruiz, C., Fernández-Checa, J. C., de Frutos, P. G., & Morales, A. (2010) · Hepatology · doi:10.1002/hep.23833 · Cited by 80
“Wild-type (WT) C57BL/6 and Gas6 / male mice, backcrossed into the C57BL/6 background (8-12 weeks), were generated and propagated as previously characterized.(22) Hepatic partial warm ischemia was performed for 90 minutes,(23) as detailed in the supporting information.”
MethodContribution of Defective PS Recognition and Efferocytosis to Chronic Inflammation and Autoimmunity
Kimani, S. G., Geng, K., Kasikara, C., Kumar, S., Sriram, G., Wu, Y., & Birge, R. B. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00566 · Cited by 78
“protects against thrombosis (21) Polymorphism positively”
Yacoub, D., Hachem, A., Théorêt, J., Gillis, M., Mourad, W. M., & Merhi, Y. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.216143 · Cited by 78
Essential role of Gas6 for glomerular injury in nephrotoxic nephritis
Yanagita, M., Ishimoto, Y., Arai, H., Nagai, K., Ito, T., Nakano, T., Salant, D. J., Fukatsu, A., Doi, T., & Kita, T. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214861 · Cited by 78
Potentiation and priming of platelet activation: a potential target for antiplatelet therapy
Gresele, P., Falcinelli, E., & Momi, S. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.05.002 · Cited by 78
Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
Huang, X., Li, Z., de Guzman, E., Robinson, P. C., Gensler, L. S., Ward, M. M., Rahbar, M. H., Lee, M., Weisman, M. H., Macfarlane, G. J., et al. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.6.3 · Cited by 75
“46 48 MERTK is not expressed on the normal lymphocytes but has been found to be expressed in a majority of lymphoblasts from patients with T-cell leukemia, certain subsets of B-cell leukemia, and mantle cell lymphoma.”
Platelets in atherothrombosis: lessons from mouse models
Nieswandt, B., Aktas, B., Moers, A., & Sachs, U. J. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01488.x · Cited by 76
Jeong, D., Irfan, M., Kim, S., Kim, S., Oh, J.-H., Park, C.-K., Kim, H., & Rhee, M. H. (2017) · Journal of Ginseng Research · doi:10.1016/j.jgr.2016.11.003 · Cited by 75
“Collagen and epinephrine, standard agonists for inducing platelet activation, have been used to study defects in platelet activation and their respective properties in in vivo thrombosis [36].”
Acidification Prevents Endothelial Cell Apoptosis by Axl Activation
D’Arcangelo, D., Gaetano, C., & Capogrossi, M. C. (2002) · Circulation Research · doi:10.1161/01.res.0000036753.50601.e9 · Cited by 73
Vitamin K‐Dependent Actions of Gas6
Bellido‐Martín, L., & de Frutos, P. G. (2008) · Vitamins and hormones · doi:10.1016/s0083-6729(07)00009-x · Cited by 73
Binder, M. D., Xiao, J., Kemper, D., Ma, G. Z. M., Murray, S. S., & Kilpatrick, T. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017727 · Cited by 70
“Animals and reagents Gas6 mice [11] were backcrossed onto the C57Bl6 background as previously described [7].”
MethodAxl inhibitors as novel cancer therapeutic agents
Shen, Y., Chen, X., He, J., Liao, D., & Zu, X. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.02.033 · Cited by 72
The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview
Wium, M., Paccez, J. D., & Zerbini, L. F. (2018) · Cells · doi:10.3390/cells7100166 · Cited by 73
“Axl is expressed near-ubiquitously [10] in various organs including the adult brain (hippocampus and cerebellum), testis, breast, bone marrow stromal cells, platelets, peripheral monocytes, and macrophages [2,35,38,39,44,45].”
BackgroundShao, W.-H., Zhen, Y., Eisenberg, R. A., & Cohen, P. L. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.06.002 · Cited by 69
Fatal hemorrhage in mice lacking γ-glutamyl carboxylase
Zhu, A., Sun, H., Raymond, R. M., Furie, B. C., Furie, B., Bronstein, M., Kaufman, R. J., Westrick, R. J., & Ginsburg, D. (2007) · Blood · doi:10.1182/blood-2006-12-064188 · Cited by 68
Signal Transduction During Platelet Plug Formation
Brass, L. F., Newman, D. K., Wannermacher, K. M., Zhu, L., & Stalker, T. J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-387837-3.00019-5 · Cited by 67
Microarray‐based understanding of normal and malignant plasma cells
Vos, J. D., Hose, D., Reme, T. X., Tarte, K., Moreaux, J., Mahtouk, K., Jourdan, M., Goldschmidt, H., Rossi, J., Cremer, F. W., et al. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00362.x · Cited by 65
Godinat, A., Park, H. M., Miller, S. C., Cheng, K., Hanahan, D., Sanman, L. E., Bogyo, M. S., Yu, A. T., Nikitin, G. F., Stahl, A., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb3007314 · Cited by 64
Irfan, M., Jeong, D., Kwon, H.-W., Shin, J.-H., Park, S., Kwak, D., Kim, T., Lee, D., Park, H.-J., & Rhee, M. H. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.06.002 · Cited by 62
Shibata, T., Habiel, D. M., Coelho, A. L., Kunkel, S. L., Lukacs, N. W., & Hogaboam, C. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302766 · Cited by 63
Genetic loss of Gas6 induces plaque stability in experimental atherosclerosis
Lutgens, E., Tjwa, M., de Frutos, P. G., Wijnands, E., Beckers, L., Dahlbäck, B., Daemen, M. J. A. P., Carmeliet, P., & Moons, L. (2008) · The Journal of Pathology · doi:10.1002/path.2381 · Cited by 61
“Experimentally-induced atherosclerosis in mice The generation of Gas6 −/− mice has been described [7].”
BackgroundSelf-citationMeyer, S. F. D., Vanhoorelbeke, K., Broos, K., Salles, I. I., & Deckmyn, H. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07233.x · Cited by 61
“…receptors in platelet aggregation was demonstrated in several studies in mice lacking either Gas6 or one of the three Gas6 receptors, providing ample evidence that Gas6 may be an attractive candidate as antiplatelet target (Angelillo-Scherrer et al, 2001, 2005; Chen et al, 2004; Gould et al, 2005).”
BackgroundSu, X., Mi, J., Yan, J., Flevaris, P., Lu, Y., Liu, H., Ruan, Z., Wang, X., Kieffer, N., Chen, S., et al. (2008) · Blood · doi:10.1182/blood-2007-09-110437 · Cited by 60
The Gas6/TAM System and Multiple Sclerosis
Bellan, M., Pirisi, M., & Sainaghi, P. P. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17111807 · Cited by 58
TAM receptors in phagocytosis: Beyond the mere internalization of particles
Burstyn‐Cohen, T., & Fresia, R. (2023) · Immunological Reviews · doi:10.1111/imr.13267 · Cited by 61
“Reduced GAS6 levels even confer protection against thrombosis, 32 liver disease, 33 and cancer metastasis.”
BackgroundStructural insights into the inhibited states of the Mer receptor tyrosine kinase
Huang, X., Finerty, P. J., Walker, J. R., Butler-Cole, C., Vedadi, M., Schapira, M., Parker, S. A., Turk, B. E., Thompson, D. A., & Dhe‐Paganon, S. (2008) · Journal of Structural Biology · doi:10.1016/j.jsb.2008.10.003 · Cited by 58
Resident Endothelial Cells Surrounding Damaged Arterial Endothelium Reendothelialize the Lesion
Itoh, Y., Toriumi, H., Yamada, S., Hoshino, H., & Suzuki, N. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207365 · Cited by 58
GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis
Law, L. A., Graham, D. K., Paola, J. D., & Branchford, B. R. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00137 · Cited by 61
“5–10μM, collagen 2μg/mL, andU46619 (thromboxane A2 analog) 10μM] (3).”
BackgroundInfluentialPlatelets: Physiology and Biochemistry
Jurk, K., & Kehrel, B. E. (2023) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0043-1777305 · Cited by 57
Animal models of venous thrombosis
Albadawi, H., Witting, A., Pershad, Y., Wallace, A., Fleck, A., Hoang, P., Khademhosseini, A., & Öklü, R. (2017) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2017.08.10 · Cited by 57
Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases
Heestermans, M., Poénou, G., Duchez, A., Hamzeh‐Cognasse, H., Bertoletti, L., & Cognasse, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113176 · Cited by 58
“the stabilization of platelet aggregates due to a disturbed inside-out signaling of αIIbβ3, resulting in protection from experimental venous thrombosis [101,102].”
BackgroundRobins, R., Lemarié, C. A., Laurance, S., Aghourian, M. N., Wu, J., & Blostein, M. D. (2012) · Blood · doi:10.1182/blood-2012-05-433730 · Cited by 56
Lafdil, F., Chobert, M.-N., Deveaux, V., Zafrani, E., Mavier, P., Nakano, T., Laperche, Y., & Brouillet, A. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.02.030 · Cited by 56
“Gas6 is known as a chemo-attractant protein for vascular smooth muscle cells [13], interfering with cell adhesion and stabilizing platelet aggregation [14].”
BackgroundJung, Y., Shiozawa, Y., Wang, J., McGregor, N., Dai, J., Park, S. I., Berry, J. E., Havens, A. M., Joseph, J., Kim, J. K., et al. (2012) · Neoplasia · doi:10.1596/neo.111740 · Cited by 55
“GAS6 Mice Homozygous GAS6 mice were originally generated by homologous recombination in the laboratory of Dr Carmeliet (University in Leuven) as described [11].”
MethodSelf-citationGrowth arrest-specific gene 6 expression in human breast cancer
Cormack, O. M., Chung, W. Y., Fitzpatrick, P., Cooke, F., Flynn, B., Harrison, M. J., Fox, E., Gallagher, E., McGoldrick, A., Dervan, P. A., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604260 · Cited by 55
“Mouse studies have shown that Gas6 is a platelet response amplifier that plays a significant role in pathological thrombosis, and that Gas6-neutralising antibodies inhibit platelet aggregation in vitro (Angelillo-Scherrer et al, 2001).”
BackgroundAXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer
Axelrod, H. D., Valkenburg, K. C., Amend, S. R., Hicks, J. L., Parsana, P., Torga, G., Marzo, A. M. D., & Pienta, K. J. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0718 · Cited by 55
“GAS6/AXL promotes platelet aggregation and activation, and AXL / mice are protected against thrombosis (39, 48).”
BackgroundTutusaus, A., Marı́, M., Ortiz-Pérez, J. T., Nicolaes, G. A. F., Morales, A., & de Frutos, P. G. (2020) · Cells · doi:10.3390/cells9102186 · Cited by 55
Franc, N. C. (2002) · Frontiers in bioscience · doi:10.2741/a841 · Cited by 54
Human vitamin K-dependentGAS6: Gene structure, allelic variation, and association with stroke
Muñoz, X., Sumoy, L., Ramírez‐Lorca, R., Villar, J. R., de Frutos, P. G., & Sala, N. (2004) · Human Mutation · doi:10.1002/humu.20025 · Cited by 53
“Gas6 and Axl are expressed by vascular endothelial cells and platelets [Angelillo-Scherrer et al., 2001; Avanzi et al., 1997; Ishimoto and Nakano, 2000; Manfioletti et al., 1993].”
BackgroundFraineau, S., Monvoisin, A., Clarhaut, J. A., Talbot, J., Simonneau, C., Kanthou, C., Kanse, S. M., Philippe, M., & Benzakour, O. (2012) · Blood · doi:10.1182/blood-2012-05-429183 · Cited by 54
The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles
Happonen, K. E., Tran, S., Mörgelin, M., Prince, R. E., Calzavarini, S., Angelillo‐Scherrer, A., & Dahlbäck, B. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.699058 · Cited by 55
“Gas6 deficiency has been shown to protect mice against thrombosis, an effect that, in addition to endothelial modulation, may be due to a direct platelet-stimulatory effect of Gas6 (40).”
BackgroundInfluentialSelf-citationGrowth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure
Lee, I. J., Hilliard, B. A., Swami, A., Madara, J., Rao, S., Patel, T., Gaughan, J., Lee, J., Gadegbeku, C. A., Choi, E. T., et al. (2012) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfs337 · Cited by 53
Surin, W., Prakash, P., Barthwal, M. K., & Dikshit, M. (2009) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2009.11.002 · Cited by 51
Novel and selective spiroindoline-based inhibitors of sky kinase
Powell, N. A., Kohrt, J. T., Filipski, K. J., Kaufman, M. D., Sheehan, D. J., Edmunds, J. E., Delaney, A. M., Wang, Y., Bourbonais, F., Lee, D., et al. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.11.036 · Cited by 50
Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells
Corno, C., Gatti, L., Lanzi, C., Zaffaroni, N., Colombo, D., & Perego, P. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160405112954 · Cited by 49
“nervous system, as well as in liver, skeletal muscle, osteoclasts, and retina [16-21].”
BackgroundFlow‐based assays for global assessment of hemostasis. Part 1: biorheologic considerations
Zwaginga, J. J., Nash, G. B., King, M. R., Heemskerk, J. W. M., Frojmovic, M. M., Hoylaerts, M., & Sakaríassen, K. S. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.02177.x · Cited by 50
Self-citationAssociation of specific haplotypes of GAS6 gene with stroke
Obach, V., de Frutos, P. G., Chamorro, Á., Muñoz, X., Hurtado, B., & Sala, N. (2007) · Thrombosis and Haemostasis · doi:10.1160/th06-12-0681 · Cited by 49
Endogenous Gas6 and Ca2+-channel activation modulate phagocytosis by retinal pigment epithelium
Karl, M., Kroeger, W., Wimmers, S., Milenkovic, V. M., Valtink, M., Engelmann, K., & Strauß, O. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.02.005 · Cited by 54
Connexin 37 Limits Thrombus Propensity by Downregulating Platelet Reactivity
Angelillo‐Scherrer, A., Fontana, P., Burnier, L., Roth, I., Sugamele, R., Brisset, A. C., Morel, S., Nolli, S., Sutter, E., Chassot, A., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.015479 · Cited by 49
Self-citationHurtado, B., Muñoz, X., Recarte-Pelz, P., García, N., Luque, A., Krupiński, J., Sala, N., & de Frutos, P. G. (2011) · Thrombosis and Haemostasis · doi:10.1160/th10-10-0630 · Cited by 48
Gas6 and the Receptor Tyrosine Kinase Axl in Clear Cell Renal Cell Carcinoma
Gustafsson, A., Boström, A.-K., Ljungberg, B., Axelson, H., & Dahlbäck, B. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007575 · Cited by 48
“However, Gas6 is not believed to harbor any coagulation properties [8,9].”
BackgroundSelf-citationGas6 Promotes Inflammatory (CCR2 hi CX3CR1 lo ) Monocyte Recruitment in Venous Thrombosis
Laurance, S., Bertin, F., Ebrahimian, T., Kassim, Y., Rys, R. N., Lehoux, S., Lemarié, C. A., & Blostein, M. D. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.308925 · Cited by 49
Novel Therapeutic Targets at the Platelet Vascular Interface
Brass, L. F., Zhu, L., & Stalker, T. J. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.161026 · Cited by 47
Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma
Waizenegger, J. S., Batalla, I. B., Weinhold, N., Meißner, T., Wroblewski, M., Janning, M., Riecken, K., Binder, M., Atanackovic, D., Taipaleenmäki, H., et al. (2014) · Leukemia · doi:10.1038/leu.2014.236 · Cited by 47
Regulation of Microvascular Thromboembolism In Vivo
Egbrink, M. G. A. O., van Gestel, M. A., Broeders, M. A. W., Tangelder, G. J., Heemskerk, J. W. M., Reneman, R. S., & Slaaf, D. W. (2005) · Microcirculation · doi:10.1080/10739680590925628 · Cited by 47
“Thick black arrows mark proposed stimulating (continuous lines) or inhibiting (interrupted lines) interactions between the L-arginine/NOS pathway and the arachidonic acid/cyclooxygenase (COX) pathway: (1) COX activation by NO, leading to enhanced PGI2 synthesis; (2) PGI-synthase activation by NO, leading to enhanced P…”
BackgroundMethodGély-Pernot, A., Coronas, V., Harnois, T., Prestoz, L., Mandairon, N., Didier, A., Berjeaud, J., Monvoisin, A., Bourmeyster, N., de Frutos, P. G., et al. (2012) · Stem Cells · doi:10.1002/stem.1045 · Cited by 48
Identification of tubby and tubby-like protein 1 as eat-me signals by phage display
Caberoy, N. B., Maiguel, D. A., Kim, Y., & Li, W. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.10.008 · Cited by 45
Fisher, P. W., Brigham-Burke, M. R., Wu, S., Luo, J., Carton, J. M., Staquet, K., Gao, W., JACKSON, S., Bethea, D., Chen, C., et al. (2005) · Biochemical Journal · doi:10.1042/bj20040859 · Cited by 45
Dahlberg, S., Ede, J., & Schött, U. (2017) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2017.1379090 · Cited by 45
“In animal experiments, Gas6-deficient mice were shown to be protected from thrombosis without any increased bleeding tendency [106].”
BackgroundMacrophage–tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands
Schmidt, T., Batalla, I. B., Schultze, A., & Loges, S. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0863-7 · Cited by 47
Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation
Jones, S., Tucker, K. L., Sage, T., Kaiser, W. J., Barrett, N. E., Lowry, P. J., Zimmer, A., Hunt, S. P., Emerson, M., & Gibbins, J. M. (2007) · Blood · doi:10.1182/blood-2007-07-103424 · Cited by 45
“HK-1 indicates hemokinin 1; hHK-1, human hemokinin; hHK-1 (4-11), a truncated version of hemokinin 1; and EKA/B, C-terminal sequence shared by endokinins A,B.”
BackgroundGas6/AXL pathway: immunological landscape and therapeutic potential
Zhai, X., Pu, D., Wang, R.-L., Zhang, J., Lin, Y., Wang, Y., Zhai, N., Peng, X., Zhou, Q., & Li, L. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1121130 · Cited by 46
“In experimental studies of NSCLC and thyroid cancer, AXL silencing inhibited xenograft growth in nude mice (51, 52).”
BackgroundRole of Gas-6 in Adipogenesis and Nutritionally Induced Adipose Tissue Development in Mice
Maquoi, E., Vörös, G., Carmeliet, P., Collen, D., & LIJNEN, H. R. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000160611.68791.c6 · Cited by 44
Self-citationTargeting the TAM Receptors in Leukemia
Huey, M., Minson, K. A., Earp, H. S., DeRyckere, D., & Graham, D. K. (2016) · Cancers · doi:10.3390/cancers8110101 · Cited by 42
“Mature megakaryocytes express all three TAM RTKs at relatively high levels [28] and expression of MERTK and AXL on platelets has been independently verified (Figure 1) [29–31].”
BackgroundEkman, C. J., Flondell-Sité, D., Gottsäter, A., Lindblad, B., & Dahlbäck, B. (2009) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2009.07.025 · Cited by 41
Self-citationCheng, C. Y., & Mruk, D. D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-417047-6.00012-0 · Cited by 44
Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review)
Zhang, G., Wang, M., Zhao, H., & Cui, W. (2017) · Oncology Letters · doi:10.3892/ol.2017.7694 · Cited by 42
Metadata
- 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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