ニュートロフィルの信号伝導中にRas関連タンパク質のカルボキシルメチル化
M R Philips1, M H Pillinger, R Staud
1Department of Medicine, New York University Medical Center, NY 10016.
Science (New York, N.Y.)
|February 12, 1993
まとめ
化学誘致剤の刺激は,中性粒子のRas関連タンパク質メチル化を増加させ,これは細胞シグナル伝達に不可欠なプロセスである. このメチル化を阻害すると,中性粒子の反応を阻害し,信号伝導とタンパク質変異を結びつける.
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.
- 免疫学 免疫学とは
背景:
- ラス関連タンパク質は,翻訳後の改変によって調節される重要なシグナル伝達分子である.
- カーボキシル末端プレニルシステイン残基のメチルエステル化により,これらのタンパク質が細胞膜に導かれる.
研究 の 目的:
- ヒト中性粒子のシグナル伝達におけるRas関連タンパク質カルボキシルメチル化の役割を調査する.
- このメチル化プロセスに対するケモアトラクタント刺激の効果を決定する.
主な方法:
- 無傷なヒト中性粒子のRas関連タンパク質カルボキシルメチル化とインビトロシステムで研究した.
- 化学吸引剤としてN-ホルミルメチオニルルキュリルフェニララニン (FMLP) を利用した.
- グアノシン-5'-O-(3-チオトリホスファート) アクティベーションおよびメチレーション阻害剤が中性粒子の機能に与える影響を評価した.
主要な成果:
- FMLPの刺激により,Rasに関連するタンパク質のカルボキシルメチル化が著しく増加しました.
- Ras関連タンパク質の活性化により,p22rac2がサイトゾールからプラズマ膜への転位を誘発した.
- プレニルシステインのカルボキシルメチル化阻害剤は,FMLPに対する中性粒子の反応を阻害した.
結論:
- 受容体媒介信号伝導は,中性粒子のRas関連タンパク質カルボキシルメチル化に直接影響する.
- カーボキシルメチル化は,キモアトラクタンによって誘発される中性粒子のシグナル伝達経路における重要なステップです.
関連する概念動画
02:38The 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...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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...
Convergence and divergence, and cross-talk between signaling pathways
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...
01:26Receptor 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...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:07MAPK 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...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...