細胞分化制御におけるcsk遺伝子の機能解析

• Project/Area Number: 06281234
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas (A)
• Allocation Type: Single-year Grants
• Research Institution: Osaka University
• Principal Investigator: 岡田 雅人 大阪大学, 蛋白質研究所, 助教授 (10177058)
• Project Period (FY): 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥44,400,000 (Direct Cost: ¥44,400,000); Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 1997: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 1996: ¥7,500,000 (Direct Cost: ¥7,500,000); Fiscal Year 1995: ¥7,500,000 (Direct Cost: ¥7,500,000); Fiscal Year 1994: ¥5,400,000 (Direct Cost: ¥5,400,000)
• Keywords: Csk / チロシンキナーゼ / Src / Raft / SH2 / Cbp / がん原遺伝子 / アデノウイルスベクター / 細胞接着 / Csk結合蛋白質 / L1 / 神経 / アストロサイト / Src型チロシンキナーゼ / P19 / PC12 / Cre-loxP / ノックアウトマウス / チロシンホスファターゼ / Srcファミリー / SH-PTP2 / Src型キナーゼ / 神経系 / ジーンターゲッティング

Research Abstract

がん原遺伝子産物であるSrc型チロシンキナーゼは、細胞の接着、移動、分化に伴う形態変化の過程において重要な細胞内情報伝達分子としてはたらくことから、多細胞動物の正常な組織構築に必須の役割を担うと考えられている。本研究は、Src型チロシンキナーゼの機能を、その制御因子であるCskを利用して解析することによって、特に細胞接着を介する増殖・分化制御および組織構築分子機構の一端を解明することを目的とする。本年度は、Cskの機能調節機構を明らかにするために、Cskに結合する蛋白質の同定を行い、その構造と機能の解析を行った。その結果、以下の成績を得た。1)CskのSH2ドメインに特異的に結合する新規チロシンリン酸化膜蛋白質Cbpを分離精製し、そのcDNAクローニングに成功した。2)Cbpは複数のチロシンリン酸化部位を細胞内ドメインにもつ、TypeIIの膜結合蛋白質であった。3)Cbpは、細胞膜ミクロドメインRaftに局在し、Src-PTKによるリン酸化を介してCskを膜にリクルートする作用を持つ。4)Cbpの強制発現により、Cskを介するSrc-PTKの活性抑制効果が増強された。以上の結果から、CskによるSrc-PTKの制御にCbpが重要な役割を担うことが示された。また、CbpがRaftに局在することから、Raftを起点とする細胞内シグナリングにおける役割が示唆された。現在、細胞接着機構におけるCbpおよびRaftの意義役割について解析を進めている。

Research Products

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