血管光滑肌细胞迁移中p27的作用 (Kip1)
1Cardiology Division, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, Mount Sinai School of Medicine, New York, NY, USA.
Circulation
|June 20, 2001
概括
循环素依赖的激酶抑制剂p27 (Kip1) 对拉帕米辛抑制平滑肌肉细胞迁移的能力至关重要. 它的缺失显著降低了拉巴胺的抗迁移作用,突出了它在调节细胞运动中的作用.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 药理学 药理学是指药理学的学科.
背景情况:
- 拉帕米辛抑制了光滑肌肉细胞 (SMC) 的增殖和迁移.
- 拉帕素的SMC增殖抑制涉及p27(Kip1) 的上调.
- p27(Kip1) 在拉帕米的抗增殖作用中起作用.
研究的目的:
- 调查p27的作用 (Kip1) 在调解拉帕米辛对SMCs的抗迁移作用.
- 确定p27(Kip1) 是否对拉帕素诱导的SMC迁移抑制至关重要.
主要方法:
- 评估Rapamycin对基本纤维细胞生长因子诱导的SMC迁移在野生类型 (WT) 和p27(Kip1)-/-) 细胞使用修改的博伊登腔室的影响.
- 评估拉巴胺对大动脉SMC在WT,p27(+/-),和p27(-/-) 小鼠中的扩散迁移的影响.
主要成果:
- 拉巴胺素剂量依赖地抑制了WT SMC迁移,但没有p27(Kip1)(-/-) SMC迁移.
- 系统性拉巴胺的使用显著抑制了WT和p27的SMC迁移,Kip1小鼠的SMC迁移明显抑制了90%.
- p27(Kip1)(-/-) 小鼠没有显著抑制SMC迁移作为对拉帕米辛的反应.
结论:
- 缺少p27 (Kip1) 减少了拉巴素对SMC迁移的抑制作用.
- p27(Kip1) 参与了控制SMC迁移的信号通路.
- p27(Kip1) 是拉帕素对光滑肌肉细胞的抗迁移作用的关键调解剂.
相关概念视频
Cell Migration
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Cancer Cell Migration through Invadopodia
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...


