低级组件驱动瘤性RTK聚变信号,没有凝结
David Gonzalez-Martinez1, Thomas R Mumford1, Delaney Wilde1
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
bioRxiv : the preprint server for biology
|December 22, 2025
概括
受体氨酸激酶 (RTK) 融合驱动癌症信号传递. 低级多元化,而不是大缩物,对于RTK融合活动和瘤信号传输是足够的.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 受体氨酸激酶 (RTK) 融合是大约5%的人类癌症的致癌驱动因素.
- 这些细胞质RTK融合激活下游信号通路的精确机制仍然不完全理解.
- 在RTK聚变信号传导中,中等尺度凝聚体与扩散组件的作用是一个关键的未解决的问题.
研究的目的:
- 阐明控制细胞质RTK融合信号传输的原则.
- 确定多元化和凝结对瘤信号的相对贡献.
- 调查是否分散组件或凝聚物对于RTK聚变活动至关重要.
主要方法:
- 使用先进的显微镜和单细胞分析.
- 合成RTK融合被设计为剖析信号机制.
- 评估了凝结,扩散信号和下游通路激活之间的相关性.
主要成果:
- 对于EML4-ALK,信号活动与扩散相比与凝结相更密切相关.
- 合成RTK融合 (ALK,RET) 诱导了Ras-Erk信号,即使没有形成凝结物.
- 低级多元化是RTK融合的普遍特征,而中尺度凝聚是罕见的,与信号传输无关.
结论:
- 低级RTK融合的多元化足以启动瘤信号.
- 凝结对于RTK聚变驱动的瘤发生是不必要的.
- 由多元化驱动的酸化是下游信号激活的关键步骤.
更多相关视频
相关概念视频
Receptor Tyrosine Kinases
17.7K
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...
17.7K
MAPK Signaling Cascades
7.8K
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...
7.8K
Interactions Between Signaling Pathways
7.1K
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...
7.1K
The Ras Gene
7.0K
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...
Ras is a...
7.0K
Assembly of Signaling Complexes
6.4K
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,...
6.4K
mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K


