SH2ドメインを持つ新しい変換タンパク質 (SHC) は,ミトゲン信号伝導に関与しています
G Pelicci1, L Lanfrancone, F Grignani
1Istituto Clinica Medica I, Policlinico Monteluce, University of Perugia, Italy.
Cell
|July 10, 1992
まとめ
新しく発見されたSHCタンパク質は,活性化された成長因子受容体を細胞増殖経路と結びつける. マウス細胞におけるSHCの過剰発現は,変異したフェノタイプと腫瘍形成を誘発し,哺乳類の細胞成長調節におけるSHCの役割を強調した.
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:
- SHC遺伝子は,Srcホモロジー2 (SH2) ドメインを含むアダプタータンパク質のファミリーをコードする.
- SHCタンパク質は,成長因子受容体によって開始される信号伝達経路に関与しています.
研究 の 目的:
- 新型SHC遺伝子とそのタンパク質産物について説明する.
- 活性化された成長因子受容体からの信号を媒介するSHCタンパク質の役割を調査する.
- 哺乳類の細胞におけるSHC過剰発現の機能的影響を決定する.
主な方法:
- SH2 DNAプローブを使用してcDNAライブラリスクリーニング.
- 抗SHC抗体を用いたウエスタン・ブロット分析.
- 細菌で発現したSHC SH2ドメインのインビトロ結合測定法.
- 裸のマウスの腫瘍形成を含むSHCを過剰発現するNIH 3T3線維芽細胞のフェノタイプ分析.
主要な成果:
- C端末SH2ドメインを持つ46.8kDaおよび51.7kDaのタンパク質をコードするSHCcDNAの分離と特徴付け.
- 哺乳類の細胞系における46,52,66 kDaのSHCタンパク質の識別.
- SHCタンパク質が活性化された表皮生長因子受容体 (EGFR) によって複合し,そして,それによりリン酸化されることを示した.
- SHC受容体との関連がin vitroで確認された.
- NIH 3T3細胞における構成性SHC過剰発現は,体内での変異と腫瘍形成につながった.
結論:
- SHC遺伝子の産物は,活性化された成長因子受容体を下流の信号伝達経路と結合させ,重要な仲介者として機能します.
- SHCタンパク質は,哺乳類の細胞増殖と腫瘍発生の調節に重要な役割を果たします.
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