Molecular Mechanism of Circadian Signal Generation in Mammals

哺乳动物昼夜节律信号产生的分子机制

基本信息

批准号：
01440024
负责人：
NAKAGAWA Hachiro
金额：
$ 16万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1992
项目状态：
已结题

项目摘要

1. Involvement of protein-tyrosine kinase (PTK) in generation of the circaadian rhythm. We found that continuous infusion of insulin into rat brain eliminated the circadian rhythms completely. From this finding, we examined the problem of whether PTK was really involved in the circadian signal generation. During the course of this investigation, we isolated a new type of PTK from neonatal rat brain and named it CSK. We showed that this enzyme specifically phosphorylates the C-terminal tyrosine residues of src-family PTKs and that it inhibited the latter activities. We obtained several lines of evidence that CSK might play critical roles in neuronal differentiation, immumne regulation and carcinogenesis. We showed that PTK activity of p60^<c-src> in the suprachiasmatic nucleus (SCN) exhibited the daily change, but we have not obtained evidence yet that CSK is specifically involved in this mechanism. 2. Relationship between rhythm generation and cell cycle. We isolated a D type G1 cyclin, a regulatory protein for cell cycle, from matured brain, in which neurons lose their proliferating abilities. We are now examining how cell cycle regulation and circadian signal generation are interconnected. 3. Central regulation of energy metabolism. It is known that the SCN is roughly divided into two parts, the dorsomedial and ventrolateral parts, and that the cicadian clock is located in the former and the retinohypothalamic tract which is involved in synchronization of the circadian period to an environmental LD cycle is projected to the latter. We found that the regulatory center for energy supply to the brain is located in the latter and obtained evidence suggesting that these functions are cooperatively regulated with the circadian signal generation.

1。蛋白 - 酪氨酸激酶（PTK）参与曲折节奏的产生。我们发现，将胰岛素连续输注到大鼠脑中完全消除了昼夜节律。从这一发现中，我们研究了PTK是否真正参与昼夜信号产生的问题。在研究过程中，我们从新生大鼠大脑中分离了一种新型的PTK，并将其命名为CSK。我们表明，这种酶特异性地磷酸化了SRC家族PTK的C末端酪氨酸残基，并抑制了后一种活性。我们获得了几条证据，表明CSK可能在神经元分化，immumne调节和致癌作用中起关键作用。我们表明，p60^<c-src>在上核核（SCN）中的PTK活性表现出每日变化，但我们尚未获得证据表明CSK特别参与了这种机制。 2。节奏生成与细胞周期之间的关系。我们从成熟的大脑中分离出D型G1 cyclin，这是一种细胞周期的调节蛋白，神经元失去了其增殖能力。我们现在正在研究细胞周期调节和昼夜节信号产生如何相互联系。 3。能量代谢的中央调节。众所周知，SCN大致分为两部分，后部和腹外侧部件，cicadian时钟位于前者，视网膜丘脑河流涉及昼夜节律时期与环境LD周期的同步。我们发现，大脑能源供应中心位于后者中，并获得了证据，表明这些功能与昼夜信号的产生协同调节。