造血因子の構造と作用の分子生物学的検討と生体内作用

• 研究課題/領域番号: 04247101
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 東京大学
• 研究代表者: 新井 賢一 東京大学, 医科学研究所, 教授 (00012782)
• 研究分担者: 高津 聖志 東京大学, 医科学研究所, 教授 (10107055) ; 井川 洋二 東京医科歯科大学, 医学部, 教授 (40085618) ; 長田 重一 (財)大阪バイオサイエンス研究所, 部長 (70114428) ; 平野 俊夫 大阪大学, 医学部, 教授 (40136718) ; 岡山 博人 東京大学, 医学部, 教授 (40111950)
• 研究期間 (年度): 1992
• 研究課題ステータス: 完了 (1992年度)
• 配分額: 34,000千円 (直接経費: 34,000千円); 1992年度: 34,000千円 (直接経費: 34,000千円)
• キーワード: 造血因子 / インターロイキン / コロニー刺激因子 / レセプター / 情報伝達 / サイトカイン / 発現クローニング / 分子生物学

研究概要

1.新井らはGM-CSFレセプターのβ鎖で初期応答遺伝子の発現と複製に必須な細胞質内領域を同定した。さらに同レセプターは線維芽細胞でも増殖シグナルを伝達することからαβ鎖に相互作用するチロシンキナーゼは血球系に特異的ではないことを示した。またcAMPとPMAに応答するIL-5遺伝子の調節領域を同定し解析した。2.間野らは血球系でGM-CSFレセプターはc-fpsと相互作用する事および低親和性レセプターがヒト戎毛癌細胞株でゴナドトロピン産生を促進することを示した。3.平野らはIL-6レセプターと会合する第三の分子の存在を示しシグナル伝達との関連について検討した。さらにjunB遺伝子のIL-6応答領域を同定し、この領域に結合するDNA結合蛋白質cDNAをクローニングした。4.長田らはG-CSFレセプターと成長ホルモンレセプターとのキメラ分子を作製しレレプターの二量体化がシグナル伝達に必須であることを示した。5.岡山らは線維芽細胞の増殖におけるc-raf-lとMAPキナーゼの関連について検討し、血清刺激に応答するc-raf-lの下流因子の遺伝子を単離した。6.高津らは低親波性IL-5レセプターα鎖cDNAをパニング法を用いてクローニングし高親和性IL-5レセプターをα鎖とGM-CSF及びIL-3レセプターの共通の成分でもあるβ鎖(AIC2B)を用いて再構成した。さらにα鎖の細胞質内ドメインのシグナル伝達への関与を示した。7。赤血球前駆細胞においてF-SFFVgp55はEPOレセプターを通して細胞増殖を活性化する。井川らはF-MCFのenvに由来するF-SFFVgp55とEPOレセプターをCTLL-2細胞に導入した。両者はBAF/3細胞では増殖シグナルを伝達するがCTLL-2では陰性であることからIL-2レセプターβ鎖とEPOレセプターの下流のシグナルは異なる事を示した。7。長田ら、高津らおよび新井らはG-CSF、IL-5、IL-3およびGM-CSFレセプターの染色体遺伝子の構造を解析した。

研究成果

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