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HUMAN PLATELET ACTIVATION AND PHOSPHOLIPID METABOLISM

人体血小板活化和磷脂代谢

基本信息

批准号：
6183639
负责人：
SUSAN E RITTENHOUSE
金额：
$ 48.14万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 2002-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6183639
关键词：
biological signal transduction complementary DNA cytoskeletal proteins enzyme activity enzyme inhibitors guanine nucleotide binding protein human tissue integrins lipid metabolism phosphatidylinositol 3 kinase phospholipids phosphorus metabolism phosphorylation platelet activation platelet aggregation polymerase chain reaction protein kinase C western blottings

项目摘要

Experiments described in this application focus on the characterization, regulation and physiological function of a relatively recently described group of kinases that act on phosphatidylinositosol. The enzymes are known as phosphoinositide 3-k (PI 3-K). Reactions involving these enzymes are monitored by radiolabeled product formation and Western blotting. Dr. Rittenhouse has carried out extensive preliminary studies with a specific inhibitor of PI 3-K activity is important for the signal cascade that culminates in the most important functional response of activated platelets-cohesion and aggregation. Inhibition of PI 3-K blocks agonist- stimulated exposure of activated glycoprotein Iib/IIIa, the integrin to which fibrinogen binds to platelets. This phenomenon has been detected by the GPIIb/IIIa antibody, known as PAC-1. Dr. Rittenhouse will study an extensive list of factors which regulate the activation and specificity of PI 3-Ks and the linkage of PI 3-Ks to the cytoskeleton. Among the factors to be studied are: Protein kinases, GTP-binding proteins, cytoskeletal components, and an important platelet protein-pleckstrin. Other preliminary experiments carried out by Dr. Rittenhouse have shown the product of PI 3-K activity, PI(3,4,5) P3, promotes protein phosphorylation when added to permeabilized platelets. The kinase(s) involved in this phosphorylation have not as yet been identified. The experiments on permeabilized platelets appear to be relevant to intact platelets, since wortmannin inhibits phosphorylation of specific proteins in activated platelets, and the addition of PI(3,4,5) P3 to permeabilized platelets overcomes the inhibitory effects of wortmannin on protein phosphorylation. Other experiment are designed to examine and characterize two new, additional PI 3-Ks:PI 3-K (theta) and PI 3-K(sigma). These experiments represent new research directions for Dr. Rittenhouse.

本应用程序中描述的实验侧重于表征，

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phosphatidylinositol 3,4,5-trisphosphate is formed from phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets.

磷脂酰肌醇 3,4,5-三磷酸由凝血酶刺激的血小板中的磷脂酰肌醇 4,5-二磷酸形成。

DOI：
10.1042/bj3010415
发表时间：
1994
期刊：
The Biochemical journal
影响因子：
0
作者：
Carter,AN;Huang,R;Sorisky,A;Downes,CP;Rittenhouse,SE
通讯作者：
Rittenhouse,SE

Inhibition of protein kinase C by staurosporine promotes elevated accumulations of inositol trisphosphates and tetrakisphosphate in human platelets exposed to thrombin.

星形孢菌素对蛋白激酶 C 的抑制促进暴露于凝血酶的人血小板中三磷酸肌醇和四磷酸肌醇的积累升高。

DOI：
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
King,WG;Rittenhouse,SE
通讯作者：
Rittenhouse,SE

Regulation of platelet phospholipase C.

血小板磷脂酶的调节 C.

DOI：
10.1098/rstb.1988.0078
发表时间：
1988
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
0
作者：
Rittenhouse,SE;Banga,HS;Sasson,JP;King,WG;Tarver,AP
通讯作者：
Tarver,AP

"Thrombin" receptor-directed ligand accounts for activation by thrombin of platelet phospholipase C and accumulation of 3-phosphorylated phosphoinositides.

“凝血酶”受体导向的配体负责凝血酶对血小板磷脂酶C的激活和3-磷酸化磷酸肌醇的积累。