CYCLIC GMP METABOLISM IN CELLULAR DEFFERENTIATION AND FUNCTION

细胞分化和功能中的循环 GMP 代谢

• 批准号: 6244668
• 负责人: JOHN Kelley BENTLEY
• 金额: $ 2.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-20 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6244668
• 关键词: 3'5' cyclic nucleotide phosphodiesterase; PC12 cells; cell differentiation; cyclic GMP; enzyme activity; gene expression; messenger RNA; molecular cloning; neurotrophic factors; nucleotide metabolism; site directed mutagenesis; sympathetic nervous system

Changes in cyclic 3':5' nucleotide (cNMP) metabolism occur in sympathetic dysfunction. Differentiation of PC12 cells into a sympathetic neuronal phenotype is accompanied by changes distinct cNMP phosphodiesterases (PDEs). Nerve growth factor (NGF) or vanadate reduce cGMP- stimulated PDE (the PDE 2 gene product) in PC12 cells by 50 % after 24 hours. NGF does not decrease PDE 2 mRNA, but increase calmodulin- stimulated PDE (the PDE 1 gene) mRNA. Sympathetic differentiation may shift cNMP metabolism from a cGMP- regulated to a calcium-regulated state. To study this 1), PDE cDNAs from PC12 cells and sympathetic ganglia will be characterized by molecular cloning and expression. 2) NGF effects on PDE mRNA and protein expression will be assessed. 3) The role of phosphorylation in the regulation of PDE activity will be determined by to be determined by phosphopeptide mapping and site directed mutagenesis and expression studies.

环状3'：5'核苷酸（CNMP）代谢的变化发生在 同情功能障碍。将PC12细胞分化为 交感神经表型伴随着不同的CNMP的变化 磷酸二酯酶（PDES）。神经生长因子（NGF）或钒酸盐降低 PC12细胞中的CGMP刺激PDE（PDE 2基因产物）50％ 24小时后。 NGF不会降低PDE 2 mRNA，而是增加 钙调蛋白刺激的PDE（PDE 1基因）mRNA。 同情 分化可能会将CNMP代谢从受调节的CGMP转移到A 钙调节状态。 为了研究此1），来自PC12细胞的PDE cDNA 和交感神经节将以分子克隆和 表达。 2）NGF对PDE mRNA和蛋白表达的影响将是 评估。 3）磷酸化在PDE调节中的作用 活性将由磷酸肽确定 映射和站点定向诱变和表达研究。