信号支架Shoc2通过抑制mTORC1-介导的IFN反应来调节淋巴血管生成
bioRxiv : the preprint server for biology
|April 8, 2025
概括
信号支架蛋白Shoc2对于淋巴血管系统的发展至关重要. 它的损失会通过破坏ERK1/2和mTORC1信号通路导致淋巴缺陷和细胞衰老.
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
- 分子遗传学 分子遗传学
背景情况:
- 淋巴血管系统的发展对于液体平衡和免疫功能至关重要.
- 淋巴发育的失调会导致先天性疾病.
- 控制淋巴血管生成的分子机制尚未完全理解.
研究的目的:
- 为了研究信号支架蛋白Shoc2在淋巴血管生成中的作用.
- 阐明Shoc2调节淋巴发育的分子机制.
主要方法:
- 在Shoc2功能丧失模型的体内研究.
- 使用淋巴内皮细胞进行体外研究.
- 分析信号通路,包括ERK1/2和mTORC1.1.
- 评估线粒体功能和先天免疫反应.
主要成果:
- 在体内,Shoc2的丧失导致了淋巴血管形成的严重缺陷.
- 在实验室中,Shoc2缺乏导致淋巴内皮细胞衰老.
- 对于正确的ERK1/2信号发送,Shoc2是必需的,并且抑制了mTORC1信号发送.
- 不调节的信号破坏了线粒体呼吸,并诱导了IRF/IFN-II反应.
- 一种Noonan综合征变异的Shoc2模仿了功能丧失的表型.
结论:
- Shoc2在淋巴血管生成中发挥着至关重要的,以前未被认可的作用.
- 冲击2信号对于维持淋巴内皮细胞功能和防止衰老至关重要.
- 在Shoc2,线粒体呼吸,先天免疫和淋巴发育之间建立了新的联系.
- 这些发现对理解和治疗与Ras通路相关的先天性疾病有影响.
相关概念视频
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
The JAK-STAT Signaling Pathway
8.5K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.5K
PI3K/mTOR/AKT Signaling Pathway
3.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.3K
Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
Interactions Between Signaling Pathways
6.2K
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...
6.2K
Amplifying Signals via Enzymatic Cascade
8.2K
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...
8.2K


