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(Received for publication, April 30, 1996, and in revised form, September 6, 1996)
From the Axl, Sky, and Mer, members of an Axl/Sky receptor
tyrosine kinase subfamily, are typified by the cell adhesion
molecule-related extracellular domain. The product of growth
arrest-specific gene 6 (Gas6), structurally homologous to
the anticoagulant protein S, was recently identified as the ligand for
Axl and Sky, but the ligand for Mer remained unknown. We have now
obtained evidence that Gas6 can also function as a ligand for Mer.
Co-precipitation analysis, using soluble receptors of Axl, Sky, and Mer
(Axl-Fc, Sky-Fc, and Mer-Fc) composed of the extracellular domain of
receptors fused to the Fc domain of immunoglobulin G1, clearly showed
that Gas6, but not protein S, specifically bound to Axl-Fc, Sky-Fc, and
Mer-Fc fusion proteins. Quantitative kinetic analyses using a BIAcore
biosensor instrument revealed dissociation constants (Kd) of the binding of rat Gas6 to Axl-Fc, Sky-Fc,
and Mer-Fc are 0.4, 2.7, and 29 nM, respectively. We also
found that Gas6 stimulated tyrosine phosphorylation of Axl, Sky, and
Mer receptors ectopically expressed in Chinese hamster ovary cells. Taken together, these findings suggest that Gas6 is a common ligand for
Axl, Sky, and Mer, all known members of an Axl/Sky receptor subfamily.
Volume 271, Number 47,
Issue of November 22, 1996
pp. 30022-30027
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
and
Department of Biology, Faculty of Science,
Kyushu University, Fukuoka 812-81, Japan, the ¶ Shionogi
Research Laboratories, Shionogi & Co., Ltd., Osaka 553, Japan, and
the 
Laboratory of Molecular Oncology, The Rockefeller
University, New York, New York 10021
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