一种新的PTH1R突变导致通过cAMP-PI3K/AKT通路导致喷发的初级失败
Kejie Lu1,2, Ying Qian1,2, Jiaxing Gong3,4
1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, China.
Progress in orthodontics
|February 23, 2025
概括
甲状腺激素1受体 (PTH1R) 基因的新奇突变通过破坏细胞信号通路,导致爆发 (PFE) 的初级失败. 这一发现澄清了PFE的遗传基础,并提供了对其分子机制的见解.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 初级喷发失败 (PFE) 是一种罕见的疾病,导致后部开口咬伤.
- 甲状腺激素1受体 (PTH1R) 基因的突变与PFE有关,但机制尚不清楚.
研究的目的:
- 在PFE家族中识别PTH1R变异.
- 阐明与PTH1R相关的PFE的致病机制.
主要方法:
- 整体外基因组测序以识别PTH1R变体.
- 细胞检测 (骨质生成,cAMP积累) 和计算分析.
- RNA测序和救援实验以验证致病途径.
主要成果:
- 在PFE家族中发现了一种新的PTH1R误解突变 (E302K).
- E302K突变损害了PTH1R与Gαs的结合,减少了cAMP的积累,并抑制了骨质生成.
- RNA测序揭示了cAMP-PI3K/AKT信号通路的下调.
结论:
- E302K PTH1R突变破坏了Gαs结合和cAMP-PI3K/AKT通路,导致骨质生成和PFE受阻.
- 这项研究扩展了已知的PFE遗传原因,并澄清了其分子病原性.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
The JAK-STAT Signaling Pathway
8.6K
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...
8.6K
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
Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
The Intrinsic Apoptotic Pathway
6.0K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.0K
The Ras Gene
6.1K
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...
6.1K


