成長因子とサイトカイン受容体によって活性化された一般的な核信号伝導経路
H B Sadowski1, K Shuai, J E Darnell
1Cold Spring Harbor Laboratory, NY 11724.
Science (New York, N.Y.)
|September 24, 1993
まとめ
皮膚表皮成長因子 (EGF) やインタールイキンなどの異なる細胞受容体は,共通の遺伝子経路を誘発することができます. これにより,細胞は特定の転写因子を選択的に活性化することによって,さまざまな信号に反応することができます.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナル伝達です.
- 遺伝子調節 遺伝子調節
背景:
- 細胞表面受容体は,成長因子やサイトカインなどの外部刺激に対する多様な細胞反応を媒介する.
- 異なる生化学的性質を持つ受容体は,共有された下流のシグナル伝達メカニズムを示し,類似またはユニークな生物学的結果を誘導することができます.
研究 の 目的:
- 異なる細胞表面受容体が共通の遺伝子セットを活性化させる方法を調査する.
- これらの反応を媒介する潜在的な細胞質転写因子の役割を理解する.
- 様々なリガンドによる遺伝子発現の微分調節の探求.
主な方法:
- 潜伏の細胞質転写因子のチロシンリン酸化を研究した.
- 異なるリガンドによって活性化された転写因子のDNA結合特性を分析した.
- 皮膚の成長因子,インターフェロン・ガンマ,インタールイキン-6による遺伝子セット活性化を比較した.
主要な成果:
- エピダーマルの成長因子,インターフェロン・ガンマ,およびインタールユーキン-6が潜伏する細胞質転写因子を活性化します.
- これらの要因は類似のDNA要素を認識し,共通の経路を示した.
- 異なるリガンドは,独特のDNA結合特異性を持つ異なった転写因子のパターンを誘導した.
- この差異的活性化は,同じ細胞型と異なる細胞型の両方で発生しました.
結論:
- 関係のない細胞表面受容体は,共通の核信号伝導経路に収束することができる.
- 潜伏中の細胞質タンパク質の差異的利用は,共通の遺伝子セットとユニークな遺伝子セットの両方の調節を可能にします.
- このメカニズムは,多種多様な細胞外信号が特定の細胞反応に変換される方法の基礎を提供します.
関連する概念動画
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...
01:15Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:20The 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...
01:16TGF - 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...
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...