为了激活EGFR,需要在血膜内侧的胆固醇与胆固醇相互作用
Do-Hyeon Kim1, Minh-Triet Hong1,2, Eduard V Bocharov3,4
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, Republic of Korea.
Science advances
|December 19, 2025
概括
血膜内部的胆固醇对人类表皮生长因子受体 (EGFR) 通过其连接体的激活至关重要. 特定的EGFR跨膜域残留物调节这种胆固醇相互作用,作为信号的关键检查点.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 信号转导通路,包括人类表皮生长因子受体 (EGFR) 通路,由血组成调节.
- 胆固醇是血膜中的关键脂质,影响受体功能和信号传递.
研究的目的:
- 为了研究内部血膜传单胆固醇在依赖联体的EGFR激活中的作用.
- 阐明胆固醇影响EGFR形状和信号的分子机制.
主要方法:
- 单分子共免疫动员用于对活细胞等离子体膜上EGFR-胆固醇相互作用的直接检查.
- 分子动力学模拟和核磁共振光谱学用于结构分析.
- 局部定向突变发生,以确定参与胆固醇结合和EGFR激活的关键残留物.
主要成果:
- 血膜内部的胆固醇对于依赖于连接体的EGFR激活至关重要.
- 胆固醇有助于EGFR二元跨膜域 (TMD) 过渡到其活性构造.
- 在EGFRTMD中的Ile640-Gly641-Leu642残留模式被确定为内叶胆固醇结合和连接体激活信号的关键.
结论:
- 胆固醇作为EGF触发EGFR激活的关键检查点.
- 了解这种胆固醇-EGFR相互作用为调节生长因子信号通路提供了洞察力.
相关概念视频
Receptor Downregulation in MVBs
2.7K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.7K
Activation of Integrins
4.9K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
4.9K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
IP3/DAG Signaling Pathway
14.2K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.2K
Receptor-mediated Endocytosis
110.3K
Overview
110.3K
Receptor-mediated Endocytosis
7.4K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
7.4K


