NIH 3T3細胞におけるRasによるシグナル伝達のメカニズム的な側面
K Zhang1, A G Papageorge, D R Lowy
1Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892.
まとめ
成長因子は,GAPやニューロフィブロミン (NF1) などのGTPアゼ活性化タンパク質を阻害することによってではなく,グアニンヌクレオチド交換を刺激することによって,活発なRas-GTPレベルを上昇させます. 細胞密度はRas-GTPレベルにも影響する.
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.
- シグナルトランスデュークション.
背景:
- Rasタンパク質は,細胞シグナル伝達の主要な調節因子である.
- Rasの活性化には,グアノシン三リン酸 (GTP) に結合することが含まれます.
- 成長因子は,複雑なメカニズムを通して Ras の活動に影響を与えます.
研究 の 目的:
- 血清と成長因子が Ras. Ras. のGTP結合形態を調節するメカニズムを調査する.
- ラス調節におけるグアニンヌクレオチド交換とGTPase活性化タンパク質 (GAP) の作用を決定する.
主な方法:
- NIH 3T3細胞における野生型および変異Rasタンパク質 (His116) の過剰発現.
- 血清および血小板由来成長因子 (PDGF) による治療.
- 異なる細胞密度でGTP結合Rasレベルを測定する.
主要な成果:
- 血清とPDGFは,正常なRasタンパク質を発現する細胞ではGTP結合Rasを増加させたが,急速に交換されるHis116変異体を発現する細胞ではそうではなかった.
- GTPに結合したRasレベルは,高密度細胞と比較して低密度細胞で高かった.
- 高い細胞密度が,GAPのような活性度の増加と相関している.
結論:
- 成長因子は,主に Ras. 上のグアニンヌクレオチド交換を刺激する.
- より高い細胞密度でのGAP活性の増加は,Ras-GTPレベルを下げるのに寄与する.
- Rasの活性化は,ミトゲンシグナル伝達と細胞環境の両方に敏感です.
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関連する概念動画
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Ras is a superfamily...
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Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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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...
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...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...


