Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases
Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases
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DOI：
10.1074/jbc.271.47.30022
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发表时间：
1996-11-22
影响因子：
4.8
通讯作者：
Mizuno, K
中科院分区：
文献类型：
--
作者：
Nagata, K;Ohashi, K;Mizuno, K
AXL、Sky和Mer是AXL/Sky受体酪氨酸激酶亚家族的成员，以细胞黏附分子相关的胞外区为代表。生长停滞特异基因6(Gas6)的产物与抗凝蛋白S在结构上同源，最近被鉴定为Ax1和Sky的配基，但Mer的配基尚不清楚。我们现在已经获得证据表明Gas6也可以作为Mer，Go-沉淀分析的配基，使用AXL，Sky和Mer(AXL-Fc，Sky-Fc和Mer-Fc)的可溶性受体(AXL-Fc，Sky-Fc和Mer-Fc)，清楚地表明这种情况，但不是与AXL-Fc，Sky-Fc和Mer-Fc融合蛋白结合的蛋白S，使用Biacore生物传感器仪器进行定量动力学分析，显示大鼠Gas6与AXL-Fc，Sky-Fc和Mer-Fc结合的解离常数(K-d)为0.4，2.7海里和29海里。我们还发现，Gas6促进了中国仓鼠卵巢细胞异位表达的Ax1、Sky和Mer受体的酪氨酸磷酸化。综上所述，这些发现表明，Gas6是Axl、Sky和Mer的共同配体，这些都是Axl/Sky受体亚家族的已知成员。
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, Go-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 Case, 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 (K-d) 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.