KY COBRE: PDGF SIGNAL TRANSDUCTION ROLE FOR ABI FAMILY KINASES IN CELL MIGRATIO

KY COBRE：ABI 家族激酶在细胞迁移中的 PDGF 信号转导作用

• 批准号: 7610708
• 负责人: RINA PLATTNER
• 金额: $ 25.22万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610708
• 关键词: ABL1 gene; Apoptosis; Cancer cell line; Cell Proliferation; Cells; Centers of Research Excellence; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytoskeletal Modeling; Development; Drug Combinations; Event; Family; Funding; Goals; Grant; Growth Factor; Institution; Internet; Malignant Neoplasms; Neoplasm Metastasis; Pathway interactions; Phosphotransferases; Platelet-Derived Growth Factor; Process; Proteins; Regulation; Research; Research Personnel; Resources; Role; Signal Pathway; Signal Transduction; Source; Stimulation of Cell Proliferation; Tumor Cell Invasion; United States National Institutes of Health; angiogenesis; c-abl Proto-Oncogenes; cancer therapy; cell motility; insight; leukemia; migration; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Growth factors induce cell proliferation, differentiation, migration, apoptosis, and angiogenesis. Regulation of these processes is extremely important as deregulation contributes to the induction and progression of malignancy. In particular, cell motility is critical for tumor invasion and metastasis, hallmarks of aggressive cancers. Growth factors control cellular events by activating proteins in a complex web of signaling pathways. Previously, we found that c-Abl, a kinase involved in the development of leukemia, is activated by platelet-derived growth factor (PDGF), and is required for mitogenesis, cytoskeletal reorganization, and migration downstream of PDGF. Signaling pathways that control cell migration are beginning to be identified, however, the pathways are not completely characterized, and cross-talk between the pathways is only beginning to be elucidated. The overall goal of this proposal is to define Abl kinase-dependent PDGF signaling pathways that control cell migration. We aim to: 1) Determine the functional significance of PDGFR-Abl kinase bidirectional signaling. 2) Identify downstream targets of Abl kinases involved in PDGFinduced cell motility. 3) Determine whether Abl kinase activity is upregulated in non-hematopoeitic cancer cell lines, and whether Abl kinases function to promote motility and/or invasion in these ce_ls. Results from these experiments will provide us with mechanistic insight into how Abl kinase deregulation contributes to cancer formation/progression, which will aid in the discovery of new drug combinations for cancer treatment.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 生长因子诱导细胞增殖，分化，迁移，凋亡和血管生成。这些过程的调节非常重要，因为放松管制有助于恶性肿瘤的诱导和进展。特别是，细胞运动对于肿瘤侵袭和转移至关重要，这是侵略性癌的标志。生长因子通过在复杂的信号通路网络中激活蛋白质来控制细胞事件。以前，我们发现C-ABL是一种参与白血病发育的激酶，由血小板衍生的生长因子（PDGF）激活，是有丝分裂发生，细胞骨架重组和PDGF下游迁移所必需的。但是，控制细胞迁移的信号通路开始被识别，但是，途径尚未完全表征，并且途径之间的串扰才开始阐明。该建议的总体目标是定义控制细胞迁移的ABL激酶依赖性PDGF信号通路。我们的目标是：1）确定PDGFR-ABL激酶双向信号传导的功能意义。 2）鉴定参与PDGF诱导细胞运动的ABL激酶的下游靶标。 3）确定在非脊椎癌细胞系中是否将ABL激酶活性上调，以及ABL激酶是否在这些CE_L中促进运动性和/或侵袭。这些实验的结果将使我们对ABL激酶放松管制如何有助于癌症的形成/进展有助于我们提供机械洞察力，这将有助于发现新的药物组合进行癌症治疗。