由PDGF诱导的内部化促进PDGFRβ在介质细胞中的蛋白质分解裂变
Marie Rubin Sander1, Agni Karolina Tsiatsiou2, Kehuan Wang2
1Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Uppsala, Sweden.
Growth factors (Chur, Switzerland)
|October 10, 2024
概括
血小板衍生生长因子受体β (PDGFRβ) 在激活和内化后经历蛋白质分解裂变. 细胞内对于这种处理至关重要,影响下游的信号通路.
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:
- 血小板衍生生长因子受体β (PDGFRβ) 信号调节细胞功能.
- PDGFRβ的降解途径,无论是溶酶体还是蛋白质体,仍然不清楚.
研究的目的:
- 为了描述联体激活PDGFRβ的蛋白质分解裂变.
- 调查影响PDGFRβ降解的因素及其对下游信号传输的影响.
主要方法:
- 用分子量分析对PDGFRβ片段进行表征.
- 研究受体内化和细胞内 (Ca2+) 在蛋白质分解处理中的作用.
- 评估蛋白酶抑制对PDGFRβ和相关信号通路酸化的影响 (例如,PLCγ,STAT3,Erk1/2,Akt).
主要成果:
- 接体激活的PDGFRβ在内部化后经过蛋白质分解分裂成~130kDa和~70kDa的碎片.
- 细胞内Ca2+化抑制PDGFRβ蛋白质分解过程.
- 蛋白酶抑制通过增加PDGFRβ,PLCγ和STAT3酸化而改变信号传递,同时降低Erk1/2酸化.
- 在纤维细胞和经历表皮-介质细胞过渡的细胞中观察到蛋白质分解裂变.
结论:
- PDGFRβ降解涉及受体内化后的依赖的蛋白质分解裂变阶段.
- 这种裂变会影响下游的信号通路,蛋白酶体抑制揭示了复杂的调节机制.
- 这些发现提供了关于细胞过程中PDGFRβ调节的见解,例如纤维细胞功能和上皮细胞-介质细胞过渡.
相关概念视频
Receptor Downregulation in MVBs
2.0K
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...
2.0K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Amplifying Signals via Enzymatic Cascade
8.3K
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...
8.3K
Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
IP3/DAG Signaling Pathway
11.9K
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...
11.9K
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


