p185neuタンパク質とEGF受容体の分子間結合は,EGF受容体の機能を調節する
1Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Cell
|June 29, 1990
まとめ
Epidermal Growth Factor Receptor (EGFR) とp185neuはEGFにさらされるとヘテロダイマーを形成する. このEGFR-p185neu複合体はEGFRに影響を与えます.
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
- 腫瘍学 腫瘍学
背景:
- 皮膜成長因子受容体 (EGFR) とp185neuは,細胞の成長と分化に関与する重要な細胞表面受容体である.
- これらの受容体を通じた異常なシグナル伝達は,様々ながんに関与しています.
研究 の 目的:
- EGFRとp185neu.の間の潜在的なヘテロディメリゼーションを調査する.
- EGFR-p185neuヘテロディメリゼーションがEGFRシグナル伝達とリガンド結合に及ぼす機能的影響を特徴づける.
主な方法:
- EGFRとp185neuを共発する細胞系にクロスリンク剤を使用した.
- 抗EGFRおよび抗p185neu抗体による免疫プレシピテーション.
- EGFに対するEGFRの親和状態を決定するスキャチャード分析.
主要な成果:
- EGFR-p185neuヘテロダイマーとして特定された高分子量複合体が観察されました.
- ヘテロディメリゼーションは,表皮成長因子 (EGF) 曝露によって誘発された.
- EGFはEGFに対する3つの親和状態 (低い,高い,非常に高い) を示した.
- 非常に高い親和性EGFRを持つ細胞は,低レベルのEGFに対して劇的な反応を示しました.
- 抗p185neu抗体による治療はp185neuをダウン調節し,非常に高い親和性EGFRの消失を引き起こしました.
- EGFとTPAは,受容体の一種または両方の受容体タイプを発現する細胞のEGFRを微分調節する.
結論:
- EGFRとp185neuは,EGFに依存するプロセスであるヘテロダイマーを形成することができます.
- EGFR-p185neuの異体化が,EGFRのEGFへの親和性とその生物学的反応に影響する.
- p185neuを標的にするとEGFRの活性が調節され,これらの受容体を共発現するがんの潜在的な治療戦略が示唆されます.
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...
Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
TGF - 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...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.


