PROTEIN SER/THR KINASE PRK AND CELL CYCLE PROGRESSION

蛋白质 Ser/THR 激酶 PRK 和细胞周期进展

• 批准号: 6124553
• 负责人: WEI DAI
• 金额: $ 3.07万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-15 至 2000-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124553
• 关键词: affinity chromatography; antisense nucleic acid; athymic mouse; breast neoplasms; cell cycle; cell cycle proteins; cell differentiation; cell growth regulation; cell proliferation; enzyme activity; flow cytometry; gene deletion mutation; gene expression; lung neoplasms; mutant; neoplasm /cancer genetics; nucleic acid sequence; phosphorylation; polymerase chain reaction; protein kinase; protein purification; southern blotting; tissue /cell culture; tumor suppressor genes; yeast two hybrid system

DESCRIPTION: (Adapted from investigator's abstract) This proposal focuses upon the role of a newly cloned serine-threonine kinase termed "prk". This kinase is homologous to the budding yeast cdc5 and Drosophila polo and moreover is strongly homologous with the previously described murine kinase fnk. Prk is most likely to be the human homolog of the murine fnk. The physiological role of this kinase has been investigated in several systems by these workers. Specifically, it has been found to enhance progesterone induced meiotic maturation of Xenopus oocytes whereas antisense prk transcripts inhibit their maturation. It is capable of rescuing a thermosensitive cdc5 mutant of Saccharomyces cerevisiae. Its cell cycle regulation has been investigated and found to peak in the late S and G2 phases. Most interestingly, its expression is activated by thrombopoietin in MO7e megakaryocyte cells and other megakaryocytic cell lines and correlated with megakaryocytic differentiation of Dami cells. Finally, it has been found to map to chromosomal locus 8p21, a region proposed to contain tumor suppressor genes. It has been found to be commonly down-regulated in lung tumors compared to normal tissues. Ectopic expression in fibroblasts reduces growth rate and there is some indication of interaction with pRB. The objectives of the proposed studies are: 1) To examine whether prk plays a role in regulating endomitosis in megakaryocytes studied by ectopic expression and by inhibition using antisense and dominant negative mutants; 2) To investigate whether prk is mutated, deleted, and/or inactivated in spontaneous lung and breast cancers; 3) To identify proteins interacting with prk through affinity purification, the yeast two-hybrid system and in vitro phosphorylation screening of an expression library.

描述：（改编自研究者摘要）本提案的重点是