LRP AND RAP IN PROTEINASE AND LIPOPROTEIN METABOLISM

蛋白酶和脂蛋白代谢中的 LRP 和 RAP

• 批准号: 2444725
• 负责人: Dudley K. Strickland
• 金额: $ 19.08万
• 依托单位: AMERICAN NATIONAL RED CROSS
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444725
• 关键词: 3T3 cells; CHO cells; binding proteins; blood lipoprotein metabolism; chemical association; colony stimulating factor; complementary DNA; cytokine; endopeptidases; gene expression; immunocytochemistry; lipoprotein lipase; low density lipoprotein; low density lipoprotein receptor; macroglobulins; macrophage; messenger RNA; protein structure function; proteoglycan; site directed mutagenesis; very low density lipoprotein; western blottings

DESCRIPTION: The Applicant is proposing to continue his studies of the structure of LRP, functional activity of this receptor, and modulation of expression. The Investigator has delineated some of the functions of this large ubiquitous cellular receptor, which intervenes in the internalization of some lipoproteins. In addition, the same receptor associates with a2-macroglobulin (a2M), and a2M-proteinase complexes and also with uPA and tPA of the fibrinolytic system. The major effort of this application is toward the characterization of the association of LRP with lipoprotein lipase and with b-VLDL and the biochemical reaction responsible for the internalization of this complex via the LRP receptor. Binding studies of LpL and of VLDL will be done using normal cell lines and cells deficient in LPR or LDL receptors. The contribution of other cellular surface components to the binding of ligands to LRP, such as proteoglycans, will also be analyzed by performing these studies in cells with low expression of proteoglycans. A second Aim consists of elucidating the role of RAP, a 30-kDa protein that associates with LRP and seems to modify its functional activity.In his third specific Aim, the Investigator is planning to study some of the regulatory mechanisms involved in the expression of LPR and RAP by cellular components of the vessel wall.

描述：申请人提议继续他的研究 LRP 的结构、该受体的功能活性和调节 的表达。 研究者已经描述了一些功能 这种大的普遍存在的细胞受体，它干预 一些脂蛋白的内化。 此外，相同的受体 与 a2-巨球蛋白 (a2M) 和 a2M-蛋白酶复合物结合， 还与纤溶系统的uPA和tPA有关。 主要努力是 该应用程序旨在表征 LRP 的关联 脂蛋白脂肪酶和 b-VLDL 的生化反应 负责通过 LRP 受体内化该复合物。 LpL 和 VLDL 的结合研究将使用正常细胞系进行 以及缺乏 LPR 或 LDL 受体的细胞。 其他人的贡献 细胞表面成分与配体与 LRP 的结合，例如 蛋白聚糖，也将通过在 蛋白多糖低表达的细胞。 第二个目标包括 阐明 RAP（一种与 LRP 相关的 30 kDa 蛋白质）的作用 并且似乎改变了它的功能活动。在他的第三个具体目标中， 研究者正计划研究一些监管机制 参与 LPR 和 RAP 细胞成分的表达 血管壁。

项目成果

Pseudomonas exotoxin-mediated selection yields cells with altered expression of low-density lipoprotein receptor-related protein.

• DOI: 10.1083/jcb.129.6.1533
• 发表时间: 1995-06
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: FITZGERALD, DJ;FRYLING, CM;ZDANOVSKY, A;SAELINGER, CB;KOUNNAS, M;WINKLES, JA;STRICKLAND, D;LEPPLA, S
• 通讯作者: LEPPLA, S

Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen.

• DOI: 10.1016/s0021-9258(18)98848-4
• 发表时间: 1991-07
• 期刊: The Journal of biological chemistry
• 作者: D. Strickland;J. Ashcom;S. Williams;F. Battey;E. Behre;K. McTigue;J. Battey;W. Argraves

Binding and degradation of thrombospondin-1 mediated through heparan sulphate proteoglycans and low-density-lipoprotein receptor-related protein: Localization of the functional activity to the trimeric N-terminal heparin-binding region of thrombospondin-1

• DOI: 10.1042/bj3180959
• 发表时间: 1996-09-15
• 期刊: BIOCHEMICAL JOURNAL
• 影响因子: 4.1
• 作者: Chen, H;Sottile, J;Mosher, DF
• 通讯作者: Mosher, DF

Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.

人类极低密度脂蛋白/载脂蛋白-E 受体的定位和调节：滋养层表达预测受体在胎盘脂质转运中的作用。

• DOI: 10.1210/endo.136.1.7828550
• 发表时间: 1995
• 期刊: Endocrinology.
• 作者: Wittmaack,FM;Gafvels,ME;Bronner,M;Matsuo,H;McCrae,KR;Tomaszewski,JE;Robinson,SL;Strickland,DK;Strauss3rd,JF
• 通讯作者: Strauss3rd,JF

Cellular catabolism of normal very low density lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is induced by the C-terminal domain of lipoprotein lipase.

正常极低密度脂蛋白通过低密度脂蛋白受体相关蛋白/α2-巨球蛋白受体的细胞分解代谢是由脂蛋白脂肪酶的C端结构域诱导的。

• 发表时间: 1994
• 期刊: The Journal of biological chemistry
• 作者: Chappell,DA;Inoue,I;Fry,GL;Pladet,MW;Bowen,SL;Iverius,PH;Lalouel,JM;Strickland,DK
• 通讯作者: Strickland,DK