Regulation of inositol phospholipid-pelated 2nd messengers

肌醇磷脂包裹的第二信使的调节

基本信息

批准号：
07044216
负责人：
KONDO Hisatake
金额：
$ 7.3万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Phosphoinositides (PI) turnover produces second messengers such as diacylglycerol (DG) and inositol triphosphate in response to external stimuli. DG acts as an activator of several forms of protein kinase C and is converted to phosphatidic acid (PA) by DG kinase. On the other hand, PA is cleaved from phosphatidylcholine and converted to DG by PA phosphatase. PA and its metabolic derivative, lysophosphatidic acid, are potent mitogens and activators. Therefore, DG kinase and PA phosphatase play crucial roles in regulation of the relative concentration of DG and PA,both of which serve as signal mediators as well as intermediates of glycerolipid synthesis.The present study disclosed for the first time the heterogeneity of DG kinase in terms of molecular structure, biochemical characteristics and gene expression localization in the brain and clarified the molecular identity of PA phosphatase : Four subtypes of DG kinase (termed type I-IV) were identified by H.Kondo (Head investigator) and h … More is group, its fifth subtype (type delta) was identified by H.Kanoh (co-investigator), its sixth subtype (type thita) by W.J.van Blitterswijk (co-investigator), its seventh by J.A.Glomset (co-investigator), while PA phosphatase (type II) was identified by H.Kanoh. The DG kinase type I is of soluble form and localized in the oligodendrocyte, but not neurons, and the absence of its expression is seen in the brain of myelin-deficient (shiverer) mice, suggesting the role in formation and maintenance of the myelin. The type II DG kinase is of membrane-associated from and localized in the medium-spiny neurons, neurons in the nucleus accumbens and olfactory tubercle, and in the endocrine cells of the pituitary inermediate lobe, suggesting the involvement in the dopaminergic transmission. The type III is localized dominantly in the Purkinje neurons and substantially in the granule cells of the cerebellum, suggesting its role in the cerebellar motor-control. The type IV is localized in the cerebral and cebellar cortical neurons, but peculiar in the molecular structure : while the former three contain two EF-hand and zinc-finger motifs in addition to the ATP-binding domain, the type IV contains no EF-hand motifs, but possesses ankyrin-like repeats. This structure has a high homology to rdgA (a gene of Drosophila inducing the retinal degeneration). A nuclear targeting motif is also contained and the transfection of this cDNA into the fibroblast results in localization of its protein in the nucleus, suggesting its role in the regulation of transcription. The delta type contains a pleckstrin homology domain and a DPH C-terminal tail homology domain, while the thita type contains three cysteine-rich domains, a proline-rich region and a pleckstrin homology domain with overlapping ras-associating domain. The DG kinase subtype by J.A.Glomset is a membrane-bound and selectively phosphrylates arachidonoyl-DG,indicating that this is specific in the PI turnover. The type II PA phosphatase is membrane-bound and its N-terminal sequence is conserved in the partial cDNA of hic53, a H O -inducible gene. Less

磷酸肌醇（PI）的营业剂会产生第二个使者，例如二维糖（DG）和三磷酸肌醇，以响应外部刺激，作为蛋白质激酶C的激活剂，并被DG激酶转化为磷脂酸（PA）手中，裂脂酰胆碱并转化为磷酸酶。本研究披露了DG激酶的第一个基因性，就分子结构，生化特征和基因在大脑中的定位而表达了分子的定位，并阐明了Pa pa pa phosshatase的同一性。由H.Kondo（主管调查员）和H ...类型Delta确定）由H.Kanoh（共同投资者）（其第六个亚型（类型Thita））通过W.J.Van Blitterswijk（Co-Investigator），其第七名，其第七次。 j.a.glomet，而h.kanoH鉴定出Paosphatase（II型），提示在髓磷脂的形成和维持中的作用。多巴胺能传播III III型在Purkinje中主要位于大脑和皮质神经元中，但在分子结构中很奇怪：而前者三个出现了两个Ef-Hand和Zinc Finger主题。 ATP结合结构域，IV型含有无手的基序，作为与RDGA的高同源性（果蝇的基因诱导视网膜变性）一个靶向基序的核心，并且将此cDNA转染到其蛋白质蛋白质的纤维化结果中，，SUG。 -DG，指示II型PA磷酸酶的特异性是膜结合的，其N末端序列在HIC53的部分Na中保守了AH O-o-诱导基因