TGFβ型I受容体のクローン化により,TGFβ型II受容体とヘテロメア複合体を形成する
P Franzén1, P ten Dijke, H Ichijo
1Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Cell
|November 19, 1993
まとめ
研究者らは,成長因子β (TGF-β) 信号伝達の変換に不可欠な新しいセリン/スレオニンキナーゼ受容体を特定しました. このTGF-β型I受容体は,細胞応答を媒介するII型受容体と複合体を形成する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- トランスフォーミング・成長因子β (TGF-β) は,細胞過程の重要な調節因子である.
- TGF-βシグナル伝達には,特定の細胞表面受容体が関与しています.
- TGF-β受容体複合体の正確な組成は調査中です.
研究 の 目的:
- TGF-βシグナル伝達に関与する新しいセリン/スレオニンキナーゼ受容体をクローンし,特徴づけること.
- TGF-β信号伝達におけるこの受容体の役割を明らかにする.
- この受容体が,既知のTGF-β型II受容体と複合体を形成するかどうかを判断する.
主な方法:
- 新型セリン/スレオニンキナーゼ受容体のcDNAクローニングと発現.
- ラジオラベル付きTGF-β1.1を用いたリガンド結合測定法
- 受容体複合体を特定するためのクロスリンク研究.
- クローンされた受容体に対する抗体を用いた免疫プレシピテーション.
- TGF-β誘発遺伝子発現を評価する機能検査.
主要な成果:
- 53 kDaのセリン/スレオニンキナーゼ受容体をコードするcDNAが分離され,構造的にはTGF-β型II受容体に似ています.
- クローンされた受容体は,TGF-β型I受容体と一致する生化学的性質を示した.
- 拘束研究により,TGF-β型I受容体の70 kDa複合体の特徴が明らかになった.
- 免疫プレシピテーションでは,70 kDa (タイプI) と94 kDa (タイプII) の受容体複合体の両方を特定しました.
- TGF-β誘発のプラズミノゲン活性化剤阻害剤1の生成を,トランスフェクション時に欠陥細胞で回復する.
結論:
- 新しいセリン/スレオニンキナーゼ受容体は,TGF-β型I受容体として機能する.
- TGF-β信号伝導は,タイプIとタイプII受容体間の異体複合体の形成を伴う.
- このヘテロメア複合体の形成は,TGF-βの生物学的効果を媒介するために不可欠です.
さらに関連する動画
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
07:05TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
Published on: February 26, 2021
関連する概念動画
Metastasis
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Transcytosis of IgG
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Introduction to Fibroblasts
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
Activation of Integrins
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 events provide an effective stimulus.
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 events provide an effective stimulus.
