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Gene Review

Gas6  -  growth arrest specific 6

Mus musculus

Synonyms: AXL receptor tyrosine kinase ligand, GAS 6, GAS-6, Gas-6, Growth arrest-specific protein 6, ...
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Disease relevance of Gas6

  • The Gas6/Axl system is implicated in several types of human cancer as well as inflammatory, autoimmune, vascular and kidney diseases [1].
  • 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 [2].
  • Essential role of Gas6 for glomerular injury in nephrotoxic nephritis [3].
  • We found less mortality and proteinuria in Gas6(-/-) mice than in wild-type mice following injection of nephrotoxic serum [3].
  • To investigate whether Gas6 is essential for progressive glomerular injury, we constructed Gas6(-/-) mice and examined the role of Gas6 in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis [3].

High impact information on Gas6

  • Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy [4].
  • Glomerular cell proliferation, glomerular sclerosis, crescent formation, and deposition of fibrin/fibrinogen in glomeruli were also reduced in Gas6(-/-) mice [3].
  • Growth-arrest specific gene 6 (Gas6) is a vitamin K-dependent growth factor for mesangial and epithelial cells [3].
  • We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions [5].
  • The carboxylation process is vitamin K dependent, and current evidence suggests that GAS6 must be gamma-carboxylated to bind and activate any of the cognate tyrosine kinase receptors [6].

Chemical compound and disease context of Gas6


Biological context of Gas6


Anatomical context of Gas6

  • In conclusion, Gas6 appears to be a unique growth factor for fibroblasts and post-translational gamma-carboxylation is necessary for its biological activity [9].
  • Like that of PS liposomes, the uptake of apoptotic cells by macrophages was also enhanced, approximately twofold, in the presence of Gas6 [10].
  • Transfection of the cDNA encoding GAS6 into 3T3 fibroblasts is sufficient to render this previously nonsupportive cell line capable of supporting long-term hematopoietic cultures [6].
  • Here, we show that expression of GAS6 is highly correlated with the capacity of bone marrow stromal cells to support hematopoiesis in culture [6].
  • Hematopoietic support by genetically engineered 3T3 is not vitamin K dependent, and soluble recombinant GAS6 does not substitute for coculturing the hematopoietic progenitors with genetically modified 3T3 cells [6].

Associations of Gas6 with chemical compounds

  • The protein product of growth arrest specific gene 6 (Gas6), is the biological ligand for the Axl subfamily of receptor tyrosine kinases [9].
  • Recombinant Gas6, containing N terminal gamma-carboxyglutamic acid residues formed from a vitamin K-dependent reaction, stimulated both DNA synthesis and proliferation of cardiac fibroblasts under serum-free conditions [9].
  • These findings suggest that Gas6 may help phagocytic cells recognize cells with PS exposed on their surfaces, which is considered to be one of the mechanisms for clearing away dying cells [10].
  • Analyses of the mechanism of the uptake of PS liposome suggested that Gas6 interacts with PS liposome via its N-terminal Gla domain and with macrophages via its C-terminal domain [10].
  • In addition, the Gas6 mRNA level in bone marrow was up-regulated by ovariectomy and was reduced by estrogen replacement [7].

Physical interactions of Gas6

  • In our previous study, we demonstrated that Gas6 specifically binds to phosphatidylserine (PS) and links Axl-expressing cells to the PS-coated surface [10].

Regulatory relationships of Gas6


Other interactions of Gas6

  • Soluble Axl is generated by ADAM10-dependent cleavage and associates with Gas6 in mouse serum [12].
  • (Cell 54 (1988) 787) identified six genes (Gas1 through Gas6) whose expressions are upregulated in serum-deprived NIH3T3 cells [13].
  • On the contrary we found that the late constitutive increase of p38 MAPK activity associated with cell death was downregulated in Gas6-treated NIH3T3 cells thus suggesting that Gas6 might promote survival by interfering with this pathway [14].
  • Taken together, the evidence presented here identifies elements involved in the Gas6 transduction pathway that are responsible for its antiapoptotic effect and suggests that Src is involved in the events regulating cell survival [15].
  • In the present study, we examined the role of Ark and its ligand, Gas6 (encoded by growth arrest-specific gene 6), in GnRH neuron migration [16].

Analytical, diagnostic and therapeutic context of Gas6


  1. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Hafizi, S., Dahlbäck, B. Cytokine Growth Factor Rev. (2006) [Pubmed]
  2. 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]
  3. 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. J. Clin. Invest. (2002) [Pubmed]
  4. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. Angelillo-Scherrer, A., Burnier, L., Flores, N., Savi, P., DeMol, M., Schaeffer, P., Herbert, J.M., Lemke, G., Goff, S.P., Matsushima, G.K., Earp, H.S., Vesin, C., Hoylaerts, M.F., Plaisance, S., Collen, D., Conway, E.M., Wehrle-Haller, B., Carmeliet, P. J. Clin. Invest. (2005) [Pubmed]
  5. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival. Vajkoczy, P., Knyazev, P., Kunkel, A., Capelle, H.H., Behrndt, S., von Tengg-Kobligk, H., Kiessling, F., Eichelsbacher, U., Essig, M., Read, T.A., Erber, R., Ullrich, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Hematopoietic progenitor cells grow on 3T3 fibroblast monolayers that overexpress growth arrest-specific gene-6 (GAS6). Dormady, S.P., Zhang, X.M., Basch, R.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Mechanism of stimulation of osteoclastic bone resorption through Gas6/Tyro 3, a receptor tyrosine kinase signaling, in mouse osteoclasts. Katagiri, M., Hakeda, Y., Chikazu, D., Ogasawara, T., Takato, T., Kumegawa, M., Nakamura, K., Kawaguchi, H. J. Biol. Chem. (2001) [Pubmed]
  8. Gas6, warfarin, and kidney diseases. Yanagita, M. Clin. Exp. Nephrol. (2004) [Pubmed]
  9. Vitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac fibroblasts. Stenhoff, J., Dahlbäck, B., Hafizi, S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. Ishimoto, Y., Ohashi, K., Mizuno, K., Nakano, T. J. Biochem. (2000) [Pubmed]
  11. A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. Wu, Y., Singh, S., Georgescu, M.M., Birge, R.B. J. Cell. Sci. (2005) [Pubmed]
  12. Soluble Axl is generated by ADAM10-dependent cleavage and associates with Gas6 in mouse serum. Budagian, V., Bulanova, E., Orinska, Z., Duitman, E., Brandt, K., Ludwig, A., Hartmann, D., Lemke, G., Saftig, P., Bulfone-Paus, S. Mol. Cell. Biol. (2005) [Pubmed]
  13. Embryonic expression patterns of the mouse and chick Gas1 genes. Lee, C.S., Fan, C.M. Mech. Dev. (2001) [Pubmed]
  14. Gas6-mediated survival in NIH3T3 cells activates stress signalling cascade and is independent of Ras. Goruppi, S., Ruaro, E., Varnum, B., Schneider, C. Oncogene (1999) [Pubmed]
  15. Requirement of phosphatidylinositol 3-kinase-dependent pathway and Src for Gas6-Axl mitogenic and survival activities in NIH 3T3 fibroblasts. Goruppi, S., Ruaro, E., Varnum, B., Schneider, C. Mol. Cell. Biol. (1997) [Pubmed]
  16. Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to p38 mitogen-activated protein kinase. Allen, M.P., Linseman, D.A., Udo, H., Xu, M., Schaack, J.B., Varnum, B., Kandel, E.R., Heidenreich, K.A., Wierman, M.E. Mol. Cell. Biol. (2002) [Pubmed]
  17. 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.L. Crit. Care Med. (2006) [Pubmed]
  18. A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody. Fisher, P.W., Brigham-Burke, M., Wu, S.J., Luo, J., Carton, J., Staquet, K., Gao, W., Jackson, S., Bethea, D., Chen, C., Hu, B., Giles-Komar, J., Yang, J. Biochem. J. (2005) [Pubmed]
  19. Gas 6 promotes Axl-mediated survival in pulmonary endothelial cells. Healy, A.M., Schwartz, J.J., Zhu, X., Herrick, B.E., Varnum, B., Farber, H.W. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  20. Growth arrest specific gene 1 is a positive growth regulator for the cerebellum. Liu, Y., May, N.R., Fan, C.M. Dev. Biol. (2001) [Pubmed]
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