在中性粒细胞的信号传导过程中,Ras相关蛋白质的碳基甲基化
M R Philips1, M H Pillinger, R Staud
1Department of Medicine, New York University Medical Center, NY 10016.
概括
化学吸引剂刺激会增加中性粒细胞中Ras相关蛋白质甲基化,这一过程对细胞信号传递至关重要. 抑制这种甲基化阻断中性粒细胞的反应,将信号传导与蛋白质修饰联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 拉斯相关蛋白质是通过翻译后修改调节的重要信号分子.
- 碳基终端前类固醇残留物的甲基化将这些蛋白质导向细胞膜.
研究的目的:
- 为了研究与Ras相关的蛋白质碳素甲基化在人类中性粒细胞信号传递中的作用.
- 为了确定化学吸引剂刺激对这种甲基化过程的影响.
主要方法:
- 在完整的人类中性粒细胞和体外系统中研究了与Ras相关的蛋白质氧甲基化.
- 作为一种化学吸引剂,利用了N-甲基-甲基-基-基氨酸 (FMLP).
- 评估了瓜诺辛-5'-O-(3-三酸盐) 激活和甲基化抑制剂对中性粒细胞功能的影响.
主要成果:
- 激发FMLP显著增加了Ras相关蛋白质的碳素甲基化.
- 激活Ras相关蛋白质诱导了p22rac2从细胞质到血的转移.
- 孕类糖甲基化抑制剂阻断了中性粒细胞对FMLP的反应.
结论:
- 受体介导的信号转导直接影响中性粒细胞中Ras相关蛋白质的碳基甲基化.
- 碳基甲基化是化学吸引剂诱导的中性粒细胞信号通路中的关键步骤.
相关概念视频
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...


