c-kit プロトオンコゲン基因のリガンドの特定

D E Williams¹, J Eisenman, A Baird

¹Department of Experimental Hematology, Immunex Corporation, Seattle, Washington 98101.

Cell

|October 5, 1990

まとめ

研究者らは,新しいマスト細胞成長因子 (MGF) を精製し,それがc-kitタンパク質に結合することを確認した. この発見は,マスト細胞の増殖と関連するシグナル伝達経路の理解を前進させる.

科学分野:

免疫学と細胞生物学について
分子および細胞腫瘍学

背景:

マスト細胞は,免疫反応やアレルギー反応において重要な役割を果たします.
マスト細胞の増殖を調節する成長因子は,治療的介入の主要な標的である.
c-kitプロトオンコゲンは,マスト細胞の発達に不可欠な受容体チロシンキナーゼをコードする.

研究の目的:

新型マスト細胞成長因子 (MGF) を精製し,特徴づけること.
MGFとc-kitプロトオンコゲンとの関係を調査する.
c-kit受容体の機能リガンドとしてのMGFを確認する.

主な方法:

ネズミのストロマル細胞系スーパーナタンからMGFの浄化.
[3H]チミジン組み込みアッセイを使用して,MGF反応に対するインタールイキン3依存性細胞系のスクリーニング.
125IラベルのMGFと免疫プレシピテーションを用いたクロスリンク研究により,リガンド受容体相互作用が確認されました.

主要な成果:

新型マスト細胞成長因子 (MGF) を精製し,そのN端アミノ酸配列を決定した.
MGF誘発の細胞系増殖は,c-kitプロトオンコゲンmRNA発現と相関しています.
MGFは,クロスリンクと免疫プレシピテーション実験を通じて,c-kit受容体のリガンドであると確認されました.

結論:

MGFは,マスト細胞の増殖を刺激する新しい成長因子です.
MGFは,c-kit受容体チロシンキナーゼのリガンドとして機能する.
この発見は,マスト細胞の調節とc-kitのシグナル伝達を理解するための分子基盤を提供します.

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