在经验性酶网络中进行的社区检测发现了信号通路的新潜在成员
Celia De Los Angeles Colomina Basanta1, Marya Bazzi2,3, Maruan Hijazi1
1Cell signaling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
PLoS computational biology
|June 23, 2023
概括
社区检测算法应用于基蛋白质组学数据,揭示了酶网络的新型组件. 这种方法通过实验室实验验证实了TTK (提米丁-提米丁激酶) 是PI3K/AKT/mTOR信号通路中的潜在新参与者.
科学领域:
- 系统生物学 系统生物学
- 分子和细胞生物学分子和细胞生物学
- 生物信息学是一种生物信息学.
背景情况:
- 蛋白质组学测量信号通路中的酶活性.
- 从蛋白质组学数据中重建酶网络是具有挑战性的,原因是有限的酸化部位定义了酶-酶关系.
研究的目的:
- 评估社区检测算法是否可以识别酶信号网络中的新组件.
- 使用蛋白组学数据,发现与正规信号通路相关的新成员.
主要方法:
- 从蛋白质组学数据重建经验性,细胞模型特定的加权激酶网络.
- 应用社区检测算法 (模块化最大化) 来识别信号社区.
- 分析了用PI3K,AKT,MEK和ERK抑制剂治疗的急性髓性白血病 (AML) 细胞的光蛋白质组数据.
- 使用来自乳腺癌细胞和湿实验室实验的外部数据集进行验证.
主要成果:
- 社区检测成功识别了已知的正规信号组件.
- 确定了TTK (提米丁-提米丁激酶) 激酶是PI3K/AKT/mTOR信号通路的潜在组成部分.
- 实验证实TTK酸化在AML细胞中随着AKT和mTOR抑制剂的治疗而降低.
结论:
- 社区检测算法是分析实证酶网络的有效工具.
- 这种方法可以发现新的组件,并扩大我们对正规信号通路的理解.
- 在PI3K/AKT/mTOR信号网络中,TTK成为一个潜在的新监管者.
相关概念视频
Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
MAPK Signaling Cascades
5.7K
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...
5.7K
Interactions Between Signaling Pathways
6.3K
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...
6.3K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Protein-protein Interfaces
12.6K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.6K


