活性化因子VIIの組織因子結合は,細胞外信号調節キナーゼ活性化による滑らかな筋肉細胞の増殖を誘発する
Plinio Cirillo1, Gaetano Calì, Paolo Golino
1Division of Cardiology, University of Naples Federico II, Italy.
Circulation
|June 3, 2004
まとめ
滑らかな筋肉細胞の組織因子 (TF) に結合する活性化因子VII (FVIIa) は,凝固剤でない経路を通じて増殖を誘発し,ERKシグナリングカスケードを活性化します.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- 血管生物学 血管生物学とは
背景:
- 組織因子 (TF) は凝固を誘発するが,細胞受容体としても作用する.
- 信号伝達と細胞増殖におけるTFの役割は調査中です.
研究 の 目的:
- TFに結合する活性化因子VII (FVIIa) が,滑らかな筋肉細胞 (SMC) の増殖を刺激するかどうかを判断する.
- FVIIa誘発のSMC増殖に関与する細胞内メカニズムを解明する.
主な方法:
- [3H]チミジン組み込みと細胞数を用いてSMC増殖を評価した.
- 活性部位阻害FVIIa (FVIIai) と反TF抗体を用いて,特異性を調べました.
- ウェスタン・ブロッティングによるp44/42ミトゲン活性化タンパク質 (MAP) キナーゼ (ERK 1/2) 経路の活性化を分析した.
- ERK経路の役割を確認するために,MEK阻害剤 (UO126) を使用しました.
主要な成果:
- FVIIaは用量依存性のSMC増殖を誘発し,FVIIaiと反-TF抗体によってブロックされました.
- FVIIaがTFに結合すると,ERK1/2経路が活性化され,ERKのリン酸化によって証明される.
- 増殖とERKのリン酸化は,FVIIaiまたは反-TF抗体治療によって廃止されました.
- MEKの阻害は,FVIIa誘発のSMC増殖を抑制し,ERK経路の関与を確認しました.
結論:
- SMCに関するTFに拘束されるFVIIaは,凝固独立のメカニズムを通じて,特に増殖を誘導します.
- この相互作用により,ERK 1/2信号経路が活性化されます.
- この発見は,凝固,炎症,動脈硬化症の間の新しい関連性を示唆しています.
関連する概念動画
Regulation of Angiogenesis and Blood Supply
2.9K
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...
2.9K
MAPK Signaling Cascades
7.3K
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...
7.3K
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
Intracellular Signaling Affects Focal Adhesions
2.8K
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...
2.8K
Vascular Spasm
4.9K
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last...
4.9K
Extrinsic and Intrinsic Pathways of Hemostasis
10.9K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
10.9K


