权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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Tyro 3和Rse）（Ohashi，et al.1994）是Axl/UFO受体酪氨酸激酶家族的成员，其在细胞外结构域中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）样重复序列。最近，Gas 6已被鉴定为Axl受体酪氨酸激酶家族的所有成员的配体; Axl、Sky和c-Mer具有不同的亲和力（按此顺序）。然而，Sky和Gas 6在神经系统中的生理功能知之甚少，尽管其在神经系统中的重要性由Sky在大脑中的结构特征和主要表达所暗示。本研究通过RNA酶保护试验（RPA）和/或原位杂交分析表明，sky和gas 6 mRNA在成年海马CA 1区至CA 3区和齿状回均有表达，并且在发育过程中表达受到类似的调控，在胚胎期表达水平较低，在发育过程中逐渐增加，在成年时达到最高水平。在成年海马的锥体层中观察到Sky-而不是Axl-免疫反应性，表明Sky和Gas 6海马在发育过程中和成年中的作用。重组大鼠Gas 6在体外可减轻血清饥饿引起的海马神经元细胞死亡，表明Gas 6是一种新的体外海马神经元营养因子。最后，在海人酸刺激后的海马和神经切断后的坐骨神经中，gas 6的表达受到调节。总之，这些发现表明Gas 6和Sky受体酪氨酸激酶在中枢和外周神经系统中的生理重要性。