B61は,ECK受容体のタンパク質チロシンキナーゼのリガンドである
T D Bartley1, R W Hunt, A A Welcher
1Amgen Inc., Thousand Oaks, California 91320-1789.
Nature
|April 7, 1994
まとめ
研究者らは,B61をECK受容体タンパク質チロシンキナーゼのタンパク質リガンドとして特定した. この発見は,受容体-リガンド相互作用の理解と,細胞信号伝達経路における潜在的な治療標的の理解を前進させる.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナリング 細胞シグナリング
- バイオケミストリー バイオケミストリー
背景:
- ECK受容体タンパク質チロシンキナーゼは,孤児受容体のEPHファミリーに属しています.
- ECK受容体の機能を理解するには,その特定のタンパク質リガンドの識別が必要です.
研究 の 目的:
- ECK受容体の内生リガンドを分離し,特定する.
- 特定されたリガンドとECK受容体間の機能的相互作用を確認する.
主な方法:
- ECK (ECK-X) の細胞外ドメインをリガンド分離のための親和性反応剤として利用した.
- 細胞培養スーパーナタンスの初期スクリーニングのために表面プラズモン共振を用いた.
- 選択された細胞系スーパーナタントからリガンドの直接浄化のための受容器親和染色学が行われました.
主要な成果:
- ECK-X親和染色を用いて,B61と指定されたタンパク質を成功裏に浄化しました.
- 再結合B61は,完ぺきな細胞におけるECK受容体の自己リン酸化を誘発することが示されました.
- B61は以前,腫瘍ネクロシス因子-alpha.によって誘発された早期応答遺伝子産物として特定されていました.
結論:
- B61は,ECK受容体タンパク質チロシンキナーゼの真のリガンドであると確認されています.
- B61の分離に使用された方法論は,EPH受容体ファミリーの他のメンバーのリガンドを発見するために適用できます.
- この研究は,ECK受容体シグナル伝達とその生物学的役割に関するさらなる研究のための基盤を提供します.
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...
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...
Cell Signaling in Plants
Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
Receptor 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...
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.
Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:


