腫瘍死滅因子によるNF-kappaBの活性化には,Aktセリン・スレオニンキナーゼが必要です
O N Ozes1, L D Mayo, J A Gustin
1Department of Microbiology and Immunology, Indiana University School of Medicine, the Walther Oncology Center, Indianapolis 46202, USA.
Nature
|September 15, 1999
まとめ
Aktセリン・スレオニンキナーゼとNF-カッパB誘導キナーゼ (NIK) は,炎症反応中に核転写因子NF-カッパBを活性化するために重要である. アクト アクト アクト
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 免疫学 免疫学とは
背景:
- 核転写因子NF-kappaBの活性化は,免疫反応と炎症反応に不可欠である.
- この活性化には通常,NF-カッパB誘導キナーゼ (NIK) とIKBキナーゼ (IKK) コンプレックスが必要です.
研究 の 目的:
- 腫瘍ネクロシス因子 (TNF) によって媒介されるNF-kappaBの活性化におけるAktセリン・スレオニンキナーゼの役割を調査する.
主な方法:
- TNF媒介によるNF-kappaB活性化を評価するためにPI(3) K阻害剤 (ウォートマンニン),支配的負のPI(3) K,およびキナーゼデッドのAktを使用しました.
- NF-kappaB活動に対する構成的に活性なAktと支配的な負のNIKの影響を調べました.
- トレオニン23でIKKalphaのAkt媒介型リン酸化を調査した 23.
主要な成果:
- TNFは,NF-kappaBの活性化に不可欠なPI(3) K/Akt経路を活性化します.
- AktとNIKは,TNF誘発によるNF-kappaB活性化に必要である.
- Aktは,NF-kappaBの活性化に重要なステップであるスレオニン23でIKKalphaを直接リン酸化する.
結論:
- Aktは,TNF誘発のNF-kappaB活性化を媒介する信号経路の不可欠な構成要素です.
- AktとNIKが関与するこの経路は,重要な免疫および炎症反応の開始に不可欠です.
さらに関連する動画
関連する概念動画
Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
The JAK-STAT Signaling Pathway
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...
NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...


