REGULATION OF CCR7 MEDIATED EVENTS IN BREAST CANCER CELLS AND IN T CELLS

乳腺癌细胞和 T 细胞中 CCR7 介导的事件的调节

• 批准号: 8168395
• 负责人: CHARLOTTE M VINES
• 金额: $ 5.45万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168395
• 关键词: Adhesions; Behavior; Binding; Breast Cancer Cell; CC chemokine receptor 7; CCL19 gene; CCL21 gene; CD18 Antigens; Cell Line; Cells; Chemotaxis; Computer Retrieval of Information on Scientific Projects Database; Data; Event; Family; Fibronectins; Funding; G Protein-Coupled Receptor Genes; Grant; Human; Institution; Integrins; Lead; Ligands; Mediating; PLC gamma1; Phospholipase; Phosphorylation; Regulation; Research; Research Personnel; Resources; Role; Signal Pathway; Signal Transduction; Source; T-Lymphocyte; United States National Institutes of Health; Vascular Cell Adhesion Molecule-1; beta-Chemokines; cell motility; chemokine; lymph nodes; migration; phospholipase C gamma; response; trafficking

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. The C-C chemokine receptor 7 (CCR7) regulates trafficking of cells to the lymph nodes in response to a gradient of chemokine ligands. T cell migration to chemokines (chemotaxis) is controlled by regulating the adhesion of integrins. Although CCR7 regulation of beta 2 integrins have been studied, the role of CCR7 in regulating other families of integrins remains poorly understood. CCR7 is a GPCR that can activate signaling events following binding of either of its two ligands, CCL19 or CCL21. Initially, to better understand the signaling pathways activated by CCR7 in T cells, we used the CCR7+ Hut78 human T cell line. Migration of Hut78 cells to CCL19 or CCL21 on ¿1 integrin ligands Fibronectin and VCAM-1 revealed different migration behaviors. Analysis of the signaling pathways revealed that activation of CCR7 by CCL19 leads to increased phosphorylation of phospholipase C gamma 1, which is thought to be an upstream regulator of ERK1/2 phosphorylation and is important in beta 1 integrin signaling. Following stimulation of CCR7 with CCL19, levels of ERK1/2 phosphorylation were increased 3-fold over basal levels. In contrast, activation of CCR7 with CCL21 led to a 2-fold reduction in the level of ERK1/2 phosphorylation. CCL19 promoted phosphorylation of CCL19 , while stimulation of CCR7 with CCL21 had no effect on phospholipase C gamma phosphorylation. These data suggest that following CCR7 binding to CCL19 or CCL21 ERK1/2 phosphorylation is differentially regulated by phospholipase C¿ which may lead to differential migration through ¿1 integrins.

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