ネズミのグルカゴン受容体の表現クローニングとシグナル伝達特性

L J Jelinek¹, S Lok, G B Rosenberg

¹ZymoGenetics Inc., Seattle, WA 98105.

Science (New York, N.Y.)

|March 12, 1993

まとめ

研究者は,血糖値の制御と糖尿病の理解に不可欠なグルカゴン受容体の補完的なDNAクローンを分離しました. この受容体はグルカゴンと結合し,細胞内cAMPとカルシウムの増加を引き起こします.

科学分野:

エンドクリノロジーエンドクリノロジー
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

背景:

グルカゴンとその受容体は,血糖ホメオスタシスの主要な調節体である.
血糖コントロールの調節不良は,糖尿病の中心にある.
グルカゴン受容体の理解は,糖尿病研究にとって不可欠です.

研究の目的:

グルカゴン受容体の補完DNA (cDNA) クロンを分離し,特徴づけること.
グルカゴン受容体によって活性化されるシグナル伝達経路を調査する.
グルカゴン受容体を,関連するGタンパク質結合受容体と比較する.

主な方法:

表現クローニング戦略は,グルカゴン受容体cDNAを分離するために採用されました.
クローンされた受容体タンパク質は腎臓の細胞系で発現した.
リガンド結合測定とセカンドメッセンジャー測定 (cAMP,カルシウム) を実施した.

主要な成果:

グルカゴン受容体の機能的な補完的なDNAクローンが成功裏に分離されました.
発現したグルカゴン受容体は,高い親和性を持つグルカゴンと結合する.
グルカゴンの結合により,アデノシン3',5'-モノフォスファート (cAMP) とカルシウムの細胞内濃度が上昇しました.
グルカゴン受容体は,カルシトニンと甲状腺ホルモン受容体と構造的に類似しています.

結論:

クローンされたグルカゴン受容体は,グルカゴンと結合できる機能性タンパク質です.
グルカゴン受容体は,シグナル伝達経路を活性化させ,cAMPとカルシウムという2種類のセカンドメッセンジャーの生成につながります.
これらの発見は,グルカゴン信号伝達とその代謝調節と糖尿病における役割を理解するための分子基盤を提供します.

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