Functional analysis of the novel brain-specific receptor tyrosine kinase "Sky"

新型脑特异性受体酪氨酸激酶“Sky”的功能分析

基本信息

批准号：
08680840
负责人：
FUNAKOSHI Hiroshi
金额：
$ 1.79万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680840/
关键词：
Molecular cloning Sky Axl c-Mer Gas6 Protein S tyrosine kinase neurotrophic tyrosine kinase receptor ProteinS survival neuron

项目摘要

Sky (also known as Tyro3 and Rse) (Ohashi, et al.1994) is a member of Axl/UFO receptor tyrosine kinase family, which has two immunoglobulin (Ig)-like repeats and two fibronectin type III (FN III) -like repeats in the extracellular domain. Recently, Gas6 has been identified as ligand for all members of Axl receptor tyrosine kinase family ; Axl, Sky and c-Mer with different affinity (in this order). However physiological function of Sky and Gas6 in the nervous system are poorly understood, despite its importance in the nervous system suggested by the structural feature and predominant expression of Sky in the brain. Here we show by RNAse protection assay (RPA) and/or by in situ hybridization analysis that sky and gas6 mRNAs were expressed in adult hippocampus from CA1 region to CA3 region and dentate gyrus.Furthermore this expression was regulated in a similar manner during development ; levels were low during embryonic stages, gradually increased during development and reaching its highest levels in the adult. Sky-but not Axl-immunoreactivity was observed in the pyramidal layr of adult hippocampus, suggesting the roles of Sky and Gas6 hippocampus during development and in the adult. Recombinant rat Gas6 attenuated hippocampal neuronal cell death caused by serum starvation in vitro, indicating that Gas6 is a novel neurotrophic factor for hippocampal neurons in vitro. Finally, gas6 showed regulated expression in the hippocampus after kainic acid stimulation and in the sciativ nerve after nerve transection. Taken together, these findings indicate the physiological importance of Gas6 and Sky receptor tyrosine kinase in both central and peripheral nervous systems.

Sky（也称为 Tyro3 和 Rse）（Ohashi 等，1994）是 Axl/UFO 受体酪氨酸激酶家族的成员，该家族具有两个免疫球蛋白 (Ig) 样重复序列和两个纤连蛋白 III 型 (FN III) 样在细胞外结构域中重复。最近，Gas6被鉴定为Axl受体酪氨酸激酶家族所有成员的配体； Axl、Sky 和 c-Mer 具有不同的亲和力（按此顺序）。然而，尽管 Sky 的结构特征和大脑中的主要表达表明了 Sky 和 Gas6 在神经系统中的重要性，但人们对 Sky 和 Gas6 在神经系统中的生理功能知之甚少。在这里，我们通过RNAse保护测定（RPA）和/或通过原位杂交分析表明，sky和gas6 mRNA在成年海马从CA1区到CA3区以及齿状回中表达。此外，这种表达在发育过程中以类似的方式受到调节；在胚胎阶段水平较低，在发育过程中逐渐升高，并在成年时达到最高水平。在成年海马的锥体层中观察到 Sky 免疫反应性，但未观察到 Axl 免疫反应性，这表明 Sky 和 Gas6 海马在发育过程中和成人中的作用。重组大鼠Gas6在体外减轻了血清饥饿引起的海马神经元细胞死亡，表明Gas6是一种新型的体外海马神经元神经营养因子。最后，在红藻氨酸刺激后，gas6 在海马中以及在神经横断后在坐骨神经中显示出调节表达。总而言之，这些发现表明 Gas6 和 Sky 受体酪氨酸激酶在中枢和周围神经系统中的生理重要性。