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Gene Review

GAS6  -  growth arrest-specific 6

Homo sapiens

Synonyms: AXL receptor tyrosine kinase ligand, AXLLG, AXSF, DKFZp666G247, FLJ34709, ...
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Disease relevance of GAS6


High impact information on GAS6

  • Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3 [4].
  • These findings warrant further evaluation of the possible therapeutic use of Gas6 inhibition for prevention of thrombosis [5].
  • Gas6 amplified platelet aggregation and secretion in response to known agonists [5].
  • In addition, we found that Gas6 antibodies inhibited platelet aggregation in vitro and protected mice against fatal thrombo embolism without causing bleeding in vivo [5].
  • 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 [5].

Chemical compound and disease context of GAS6

  • Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl [6].
  • Furthermore, "trapping" Gas6 prevents pathological thrombosis, which indicates that blocking this novel cross-talk between the Gas6-Rs and alpha(IIb)beta(3) integrin may constitute a novel target for antithrombotic therapy [7].
  • 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 [5].
  • Moreover, in a mouse model of thrombosis, administration of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight similar to clopidogrel but, unlike clopidogrel, produced no increase in template bleeding [8].
  • To test whether stimulation of Axl can enhance survival of uveal melanoma cells, we assessed the degree of mitogenesis and cell survival by bromodeoxyuridine incorporation and trypan blue exclusion, respectively, upon stimulation of Mel 290 uveal melanoma cells with Gas6 in vitro [9].

Biological context of GAS6


Anatomical context of GAS6


Associations of GAS6 with chemical compounds


Regulatory relationships of GAS6


Other interactions of GAS6

  • In order to demonstrate evidence for an autocrine regulation of growth in permanent hematopoietic cell lines, we measured the GAS6 expression in cell lines with strong positivity for the AXL/UFO receptor mRNA [1].
  • Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer [19].
  • Protein S and a structurally similar protein, Gas6, have been found to stimulate members of the Axl/Sky family of receptor tyrosine kinases [20].
  • Assignments of the GAS6, POSTN and EFNB2 genes to SSC11 by somatic cell and radiation hybrid panels [21].
  • One of the most interesting aspects of this hypothetical protein is that its Gla domain is highly homologous to the Gla domain of Gas6, a ligand for Axl, while its receptor tyrosine kinase domain is highly homologous to Axl [22].

Analytical, diagnostic and therapeutic context of GAS6


  1. Expression of the growth arrest-specific gene 6 (GAS6) in leukemia and lymphoma cell lines. Dirks, W., Rome, D., Ringel, F., Jäger, K., MacLeod, R.A., Drexler, H.G. Leuk. Res. (1999) [Pubmed]
  2. Coexpression of Gas6/Axl in human ovarian cancers. Sun, W., Fujimoto, J., Tamaya, T. Oncology (2004) [Pubmed]
  3. GAS6 is an estrogen-inducible gene in mammary epithelial cells. Mo, R., Tony Zhu, Y., Zhang, Z., Rao, S.M., Zhu, Y.J. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  4. Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Godowski, P.J., Mark, M.R., Chen, J., Sadick, M.D., Raab, H., Hammonds, R.G. Cell (1995) [Pubmed]
  5. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Angelillo-Scherrer, A., de Frutos, P., Aparicio, C., Melis, E., Savi, P., Lupu, F., Arnout, J., Dewerchin, M., Hoylaerts, M., Herbert, J., Collen, D., Dahlbäck, B., Carmeliet, P. Nat. Med. (2001) [Pubmed]
  6. Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl. Ito, M., Nakashima, M., Nakayama, T., Ohtsuru, A., Nagayama, Y., Takamura, N., Demedchik, E.P., Sekine, I., Yamashita, S. Thyroid (2002) [Pubmed]
  7. Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization. Saller, F., Burnier, L., Schapira, M., Angelillo-Scherrer, A. Blood Cells Mol. Dis. (2006) [Pubmed]
  8. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. Gould, W.R., Baxi, S.M., Schroeder, R., Peng, Y.W., Leadley, R.J., Peterson, J.T., Perrin, L.A. J. Thromb. Haemost. (2005) [Pubmed]
  9. Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. van Ginkel, P.R., Gee, R.L., Shearer, R.L., Subramanian, L., Walker, T.M., Albert, D.M., Meisner, L.F., Varnum, B.C., Polans, A.S. Cancer Res. (2004) [Pubmed]
  10. Assignment of the human GAS6 gene to chromosome 13q34 by fluorescence in situ hybridization. Saccone, S., Marcandalli, P., Gostissa, M., Schneider, C., Della Valle, G. Genomics (1995) [Pubmed]
  11. Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke. Muñoz, X., Sumoy, L., Ramírez-Lorca, R., Villar, J., de Frutos, P.G., Sala, N. Hum. Mutat. (2004) [Pubmed]
  12. Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor. Gallicchio, M., Mitola, S., Valdembri, D., Fantozzi, R., Varnum, B., Avanzi, G.C., Bussolino, F. Blood (2005) [Pubmed]
  13. Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis. Sun, W.S., Misao, R., Iwagaki, S., Fujimoto, J., Tamaya, T. Mol. Hum. Reprod. (2002) [Pubmed]
  14. GAS6 inhibits granulocyte adhesion to endothelial cells. Avanzi, G.C., Gallicchio, M., Bottarel, F., Gammaitoni, L., Cavalloni, G., Buonfiglio, D., Bragardo, M., Bellomo, G., Albano, E., Fantozzi, R., Garbarino, G., Varnum, B., Aglietta, M., Saglio, G., Dianzani, U., Dianzani, C. Blood (1998) [Pubmed]
  15. The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. Shankar, S.L., O'Guin, K., Cammer, M., McMorris, F.A., Stitt, T.N., Basch, R.S., Varnum, B., Shafit-Zagardo, B. J. Neurosci. (2003) [Pubmed]
  16. Continuous signaling via PI3K isoforms beta and {gamma} is required for platelet ADP receptor function in dynamic thrombus stabilization. Cosemans, J.M., Munnix, I.C., Wetzker, R., Heller, R., Jackson, S.P., Heemskerk, J.W. Blood (2006) [Pubmed]
  17. Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Chen, J., Carey, K., Godowski, P.J. Oncogene (1997) [Pubmed]
  18. The C-mer gene is induced by Epstein-Barr virus immediate-early protein BRLF1. Li, Y., Mahajan, N.P., Webster-Cyriaque, J., Bhende, P., Hong, G.K., Earp, H.S., Kenney, S. J. Virol. (2004) [Pubmed]
  19. Structural basis for Gas6-Axl signalling. Sasaki, T., Knyazev, P.G., Clout, N.J., Cheburkin, Y., Göhring, W., Ullrich, A., Timpl, R., Hohenester, E. EMBO J. (2006) [Pubmed]
  20. Stimulation of Sky tyrosine phosphorylation by bovine protein S--domains involved in the receptor-ligand interaction. Nyberg, P., He, X., Härdig, Y., Dahlback, B., García de Frutos, P. Eur. J. Biochem. (1997) [Pubmed]
  21. Assignments of the GAS6, POSTN and EFNB2 genes to SSC11 by somatic cell and radiation hybrid panels. Ma, H., Liu, X., Shi, Q., He, C., Yerle, M., Ren, H., Li, K. Anim. Genet. (2005) [Pubmed]
  22. Identification of a gene encoding a typical gamma-carboxyglutamic acid domain in the tunicate Halocynthia roretzi. Wang, C.P., Yagi, K., Lin, P.J., Jin, D.Y., Makabe, K.W., Stafford, D.W. J. Thromb. Haemost. (2003) [Pubmed]
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