GCKR MEDIATED SIGNAL TRANSDUCTION AND LEUKEMIC TRANSFORM

GCKR 介导的信号转导和白血病转化

• 批准号: 2896405
• 负责人: JOSEPH M TUSCANO
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2896405
• 关键词: animal genetic material tag; athymic mouse; biological signal transduction; chronic myelogenous leukemia; enzyme activity; gene induction /repression; genetically modified animals; human genetic material tag; human tissue; neoplasm /cancer genetics; neoplastic transformation; oncogenes; protein kinase; receptor; tissue /cell culture

DESCRIPTION (Applicant's Description): Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of the primitive hematopoietic stem cell. CML accounts for approximately 25% of all adult leukemia. The BCR-ABL oncogene probably represents the initiating event in nearly all CML, although additional genetic events are required for the full malignant phenotype. The recently described serine-threonine kinases GCK and GCKR are known to activate the pathway that is thought to mediate the transforming ability of BCR-ABL. Specifically, based on work that is to be presented under Preliminary Studies, the applicants hypothesize that GCKR specifically associates with, and is activated by, BCR-ABL and is likely a critical element in BCR-ABL's transforming potential. Based on this they propose to: 1) examine the basic elements and requirements that mediate the association between GCKR and BCR-ABL; 2) examine the functional consequences of the BCR-ABL relationship with GCKR; 3) assess the in vivo transforming potential of GCK and GCKR. Elucidating the role of GCKR in BCR-ABL mediated transformation will allow for a better understanding of the mechanism of oncogenic transformation, and thus allow for the development of improved treatment and prognostication strategies for CML. The applicant's training in molecular biology, immunology, and clinical oncology, in addition to his direct experience with the initial cloning of GCKR put him in the unique position to pursue the studies proposed here.

描述（申请人描述）：