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Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
細胞外信号調節キナーゼ2 2の活性化におけるp21rasの関与
A M de Vries-Smits1, B M Burgering, S J Leevers
1Laboratory for Physiological Chemistry, University of Utrecht, The Netherlands.
Nature
|June 18, 1992
まとめ
細胞外信号調節キナーゼ (ERKs) のRasプロトオンコゲン産物 (Ras) 活性化は,成長因子シグナル伝達に極めて重要です. Rasはインスリンと血小板由来成長因子 (PDGF) 誘発のERK活性化を媒介する.
科学分野:
- 細胞の信号伝達経路は,
- 分子生物学は分子生物学である.
- 腫瘍遺伝子の研究
背景:
- 成長因子は,細胞外信号調節キナーゼ (ERK) を活性化させ,MAPキナーゼとも呼ばれる.
- また,成長要因がp21ras (Ras) を活性化させ,GDP型からGTP型への変換を促進します.
- p21rasオンコタンパク質の直接導入は,ERKsを迅速に活性化させ,成長因子シグナル伝達におけるその役割を示唆する.
研究 の 目的:
- 成長因子誘発のERK活性化を媒介するp21rasの役割を調査する.
- Rasが異なる成長因子シグナル伝達経路の共通のメディエーターであるかどうかを判断する.
主な方法:
- p21ras (RasAsn17) の干渉変異体を発現する再結合ワクチンウイルスを使用した.
- NIH3T3細胞におけるインスリン誘発のERK2およびフォスファディチルイノシトール3キナーゼ活性化に対するRasAsn17の効果を評価した.
- ラット-1細胞における血小板由来成長因子 (PDGF) とホルボールエステルによって誘発されるERK2活性に対するRasAsn17の影響を調査した.
主要な成果:
- RasAsn17は,インスリン受容体を過剰発現するNIH3T3細胞におけるインスリン誘発のERK2活性化を完全に抑制しました.
- RasAsn17は,インスリン誘発のフォスファディチルイノシトール-3キナーゼ活性化を阻害しませんでした.
- RasAsn17は,ラット-1細胞におけるPDGF誘発のERK2活性を抑制したが,ホルボールエステル誘発のERK2活性を抑制しなかった.
結論:
- p21ras (Ras) は,インスリンとPDGFのシグナル伝達経路における重要なメディエーターです.
- Rasは,特にこれらの成長因子によってERK2の活性化を媒介する.
- この発見は,特定の成長因子受容体とERKの活性化との関連付けにおけるRasの中心的な役割を強調しています.
関連する概念動画
The Ras Gene
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Convergence and divergence, and cross-talk between signaling pathways
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MAPK Signaling Cascades
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...
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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...
PI3K/mTOR/AKT Signaling Pathway
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 rapamycin-insensitive companion...

