トランスメブランTGF-alpha前駆体はEGF/TGF-alpha受容体を活性化する
R Brachmann1, P B Lindquist, M Nagashima
1Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Cell
|February 24, 1989
まとめ
成長因子アルファ (TGF-alpha) のトランスメブラン型前駆体は,表皮成長因子 (EGF) 受容体を活性化させます. これらの膜に結合したTGF-α形態は細胞の成長を促進し,増殖組織における細胞間通信に役割を果たす可能性があります.
科学分野:
- 細胞生物学 細胞生物学
- 分子信号伝達です.
- がん研究 がん研究
背景:
- 変形成長因子アルファ (TGF-alpha) と表皮成長因子 (EGF) は,共通の受容体を活性化する関連成長因子です.
- タンパク質分裂により溶解性TGF-αが放出されますが,細胞表面にも膜に結合した形態があります.
研究 の 目的:
- 膜に結合したTGF-α前駆体形態の生物学的活性を調べる.
- これらの形態がEGF/TGF-α受容体を活性化し,細胞増殖に影響を与えるかどうかを判断する.
主な方法:
- 分裂を防ぐためにTGF-alpha前駆体の遺伝子改変.
- 受容体陰性細胞における改変したcDNAの過剰発現.
- TGF-α形態の部分浄化とN端末配列化.
- 受容体自己リン酸化とアンカレーズ独立の細胞増殖を測定する.
主要な成果:
- 2つのトランスメブラン性TGF-α前駆体形態が特定されました.
- これらの形態は,受容体過剰発現細胞におけるEGF/TGF-α受容体のチロシン自己リン酸化を誘導した.
- 溶解した前駆物質は,フィブロブラストのアンカレージ独立の成長を促した.
- 細胞と細胞の接触も受容体の活性化につながった.
結論:
- トランスメンブレーンTGF-α前駆体形態は生物学的活性を持っています.
- 彼らはEGF/TGF-α受容体を活性化し,細胞増殖を刺激することができます.
- これらの発見は,増殖組織内の細胞-細胞の相互作用において,膜に結合したTGF-αの役割を示唆する.
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