CSF-1R Regulation of Type I PIP5K

I 型 PIP5K 的 CSF-1R 调节

• 批准号: 0235028
• 负责人: Nathan Davis
• 金额: $ 16.5万
• 依托单位: LSU Health Sciences Center -Shreveport
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2005-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0235028&HistoricalAwards=false
• 关键词: CSF; 1R; Regulation; Type; PIP5K

A grant has been awarded to Dr. J. Nathan Davis of Louisiana State University Health Sciences Center in Shreveport for the study of the beta isoform of phosphatidylinositol 4-phosphate 5-kinase (mPIP5K-Ibeta), an enzyme involved in the metabolism of the membrane lipid, phosphatidylinositol (PtdIns). PtdIns regulates diverse cellular processes including survival and proliferation, receptor internalization, membrane trafficking, secretion, and remodeling of cell structure. Such diversity of function is due to the addition of phosphate groups at specific sites on the inositol ring by specific PtdIns kinases. Dr. Davis's studies are designed to define the mechanisms by which hormones and growth factors regulate the activity of mPIP5K-Ibeta. Previous studies have shown that mPIP5K-Ibeta is required for the proper internalization of activated growth factor receptors using both the colony stimulating factor-1 receptor (CSF-1R) and the epidermal growth factor receptor (EGFR). One aim of this proposal is to define the molecular interactions between mPIP5K-Ibeta and these growth factor receptors. A second series of experiments are designed to examine the role of another membrane lipid, phosphatidic acid (PA), in the regulation of mPIP5K-Ibeta. The studies undertaken by Dr. Davis concern the basic regulation of an enzyme that is central to cellular PtdIns metabolism. All nucleated cells (animal, plant and fungal cells) express isoforms of the type I phosphatidylinositol 4-phosphate 5-kinase and PtdIns metabolism is essential to these cells. The ubiquitous and essential nature of PtdIns metabolism makes PtdIns synthesis a prime target for generation of cytocidal agents through the design of chemicals that specifically inhibit or activate certain classes of these enzymes. The targeting of fungal enzymes could produce agents useful in food preservation, the agricultural industry to combat fungal infections of plants and animals or in healthcare for antifungal chemotherapy. Small molecule inhibitors of plant specific enzymes are potential herbicides lacking toxicity to other organisms. However, detailed understanding of all the enzymes involved must be obtained before these goals are realized.

位于什里夫波特的路易斯安那州立大学健康科学中心的J.Nathan Davis博士获得了一项资助，用于研究磷脂酰肌醇4-磷酸5-激酶(mPIP5K-Ibeta)的β亚型，这是一种参与膜脂磷脂酰肌醇(PtdIns)代谢的酶。PtdIns调节多种细胞过程，包括生存和增殖、受体内化、膜运输、分泌和细胞结构重塑。这种功能的多样性是由于特定的PtdIns激酶在肌醇环上的特定位置增加了磷酸基团。戴维斯博士的研究旨在确定激素和生长因子调节mPIP5K-Ibeta活性的机制。以前的研究表明，mPIP5K-Ibeta是利用集落刺激因子-1受体(CSF-1R)和表皮生长因子受体(EGFR)正确内化激活的生长因子受体所必需的。这项建议的目的之一是确定mPIP5K-Ibeta与这些生长因子受体之间的分子相互作用。第二系列实验旨在研究另一种膜脂--磷脂酸(PA)在调节mPIP5K-Ibeta中的作用。戴维斯博士进行的研究涉及一种对细胞PtdIns新陈代谢至关重要的酶的基本调节。所有有核细胞(动物、植物和真菌细胞)都表达I型磷脂酰肌醇4-磷酸-5-激酶的亚型，而PtdIns的代谢对这些细胞是必不可少的。PtdIns代谢的无处不在和必不可少的性质使PtdIns的合成成为通过设计专门抑制或激活某些类别的这些酶的化学物质来产生细胞杀菌剂的主要目标。以真菌酶为靶点可能会产生有助于食品保存、农业行业抗击动植物真菌感染或用于抗真菌化疗的医疗保健的试剂。植物专一性酶的小分子抑制剂是对其他生物无毒性的潜在除草剂。然而，在实现这些目标之前，必须对所有涉及的酶进行详细的了解。