Nature 373, 623 - 626 (16 February 1995); doi:10.1038/373623a0

Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6

Brian C. Varnum^*, Cynthia Young^*, Gary Elliott^*, Andy Garcia^*, Timothy D. Bartley^*, Yih-Woei Fridell^†, Robert W. Hunt^*, Geraldine Trail^*, Chris Clogston^*, Robert J. Toso^*, Donna Yanagihara^*, Larry Bennett^*, Maura Sylber^*, Lee Anne Merewether^*, Alice Tseng^*, Eva Escobar^*, Edison T. Liu^† & Harvey K. Yamane^*

^*Amgen Inc., Amgen Center, Thousand Oaks, California 91320-1789, USA
^†Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 2759-7295, USA

THE Axl receptor tyrosine kinase was identified as a protein encoded by a transforming gene from primary human myeloid leukaemia cells by DNA-mediated transformation of NIH 3T3 cells^1–3. Axl is the founding member of a family of related receptors that includes Eyk⁴, encoded by a chicken proto-oncogene originally described as a retroviral transforming gene, and c-Mer⁵, encoded by a human protooncogene expressed in neoplastic B- and T-cell lines. The transforming activity of Axl demonstrates that the receptor can drive cellular proliferation. The function of Axl in non-transformed cells and tissues is unknown, but may involve the stimulation of cell proliferation in response to an appropriate signal, namely a ligand that activates the receptor. We report here the purification of an Axl stimulatory factor, and its identification as the product of growth-arrest-specific gene 6 (ref. 6). This is, to our knowledge, the first description of a ligand for the Axl family of receptors.

References

1.	Liu, E., Hjelle, B. & Bishop, J. M. Proc. natn. Acad. Sci. U.S.A. 85, 1952 (1988). | ChemPort |
2.	O'Bryan, J. P. et al. Molec. cell. Biol. 11, 5016−5031 (1990).
3.	Janssen, J. W. G. et al. Oncogene 6, 2113−2120 (1991). | PubMed | ISI | ChemPort |
4.	Jia, R. & Hanafusa, H. J. biol. Chem. 269, 1839−1844 (1994). | PubMed | ISI | ChemPort |
5.	Graham, D. K., Dawson, T. L., Mullaney, D. L., Snodgrass, H. R. & Earp, H. S. Cell Growth Differ. 5, 647−657 (1994). | PubMed | ISI | ChemPort |
6.	Manfioletti, G., Brancolini, C., Avanzi, G. & Schneider, C. Molec. cell. Biol. 13, 4976−4985 (1993). | PubMed | ChemPort |
7.	Fausset, P. R. & Lu, H. S. Electrophoresis 12, 22−27 (1991). | Article | PubMed | ChemPort |
8.	Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387−395 (1984). | PubMed | ISI | ChemPort |
9.	Lundwall, A. et al. Proc. natn. Acad. Sci. U.S.A. 83, 6716−6720 (1986). | ChemPort |
10.	Wu, S-M., Cheung, W-F., Frazier, D. & Stafford, D. W. Science 254, 1634−1636 (1991). | PubMed | ChemPort |
11.	Fagerstam, L. Tech. Protein Chem. 2, 65−71 (1991).
12.	Johnsson, B., Lofas, S. & Lindquist, G. Analyt. Biochem. 198, 268−277 (1991). | PubMed | ChemPort |
13.	Gasic, G. P., Arenas, C. P., Gasic, T. B. & Gasic, G. J. Proc. natn. Acad. Sci. U.S.A. 89, 2317−2320 (1992). | ChemPort |
14.	O'Bryan J. P., Fridell, Y.-W., Koski, R., Varnum, B. & Liu, E. T. J. biol. Chem. 270, 551−557 (1995). | PubMed |
15.	DeClerck, Y. A., Yean, T.-D., Lu, H. S., Ting, J. & Langley, K. L. J. biol. Chem. 226, 3893−3899 (1991).