RETINOIDS, M6P/IGF II RECEPTOR & CELL GROWTH REGULATION

类维生素A、M6P/IGF II 受体

• 批准号: 6489160
• 负责人: JING X KANG
• 金额: $ 27.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489160
• 关键词: SDS polyacrylamide gel electrophoresis; affinity chromatography; affinity labeling; animal tissue; autoradiography; binding sites; cell growth regulation; confocal scanning microscopy; electron microscopy; fluorescence microscopy; growth factor receptors; high performance liquid chromatography; immunoelectron microscopy; immunologic assay /test; immunoprecipitation; insulinlike growth factor; mannose 6 phosphate; polymerase chain reaction; protein purification; protein sequence; protein structure function; receptor binding; retinoid binding proteins; retinoids; western blottings

Both retinoids and the mannose 6-phosphate/insulin-like growth factor-II (M6P/IGF2) receptor have been shown to play fundamental roles in the control of cell growth in development and oncogenesis. Recent work has discovered that retinoic acid (RA) binds to the M6P/IGF2 receptor with high affinity, leading to alteration of the primary functions of the receptor and suppression of cell growth. These findings suggest that M6P/IGF2 receptor mediates a novel RA response pathway that may be important in cell growth regulation. However, the molecular mechanism underlying this pathway remains largely unknown. Thus, the overall goal of this proposal is to understand how RA interacts with the M6P/IGF2 receptor and the role of this interaction in cell growth regulation. The key questions that we wish to address are: 1) Where is the functional domain of the receptor protein responsible for retinoid binding? 2) What is the authentic biological consequence of the interaction? and 3) How do they work? Accordingly, the specific aims of this application are: (1) To identify the retinoid binding site of the M6P/IGF2 receptor; (2) To extend the understanding of the biological consequence of the RA-M6P/IGF2R interaction. (3) To identify the biochemical processes responsible for the biological effect of RA-M6P/IGF2R interaction. Our general approach is to create a mutant M6P/IGF2R that fails to bind RA and then assess differences of functional responses to RA between the cells expressing wild-type M6P/IGF2R and those with the mutant receptor. The principal methods to be used include protein mutagenesis, photoaffinity labeling, amino acid sequence analysis, ligand binding assay, immuno-detection, enzymatic assay and morphological analysis. Significance This project will provide fundamental information about how retinoids interact with the M6P/IGF2 receptor and shed light on the role of this novel retinoid-response pathway in regulation of cell growth. This knowledge may lead to novel or more effective therapeutic and preventive approaches for cancer and developmental defects.

类维生素a和甘露糖6-磷酸/胰岛素样生长

项目成果

Differential expression of the mannose 6-phosphate/ insulin-like growth factor-II receptor in human breast cancer cell lines of different invasive potential.

不同侵袭潜力的人乳腺癌细胞系中甘露糖 6-磷酸/胰岛素样生长因子-II 受体的差异表达。

• 发表时间: 2002
• 期刊: Medical science monitor : international medical journal of experimental and clinical research.
• 作者: Xie,Suqing;Kang,JingX
• 通讯作者: Kang,JingX

Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells.

• 发表时间: 2002-03
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Y. Ge;Zhihong Chen;Z. B. Kang;J. Cluette-Brown;M. Laposata;J. Kang

The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene transfer of omega-3 fatty acid desaturase.

• DOI: 10.1159/000073790
• 发表时间: 2003
• 期刊: World review of nutrition and dietetics
• 作者: J. Kang

Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes.

• DOI: 10.1186/1471-2121-5-15
• 发表时间: 2004-04-28
• 期刊: BMC cell biology
• 作者: Chen Z;Ge Y;Kang JX
• 通讯作者: Kang JX

Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids.

甘露糖 6-磷酸/胰岛素样生长因子 II 受体介导类视黄醇的生长抑制作用。

• 发表时间: 1999
• 期刊: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.
• 作者: Kang,JX;Bell,J;Beard,RL;Chandraratna,RA
• 通讯作者: Chandraratna,RA