Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains

• Tanaka, Hiroaki

• Akagi, Ken-ichi

• Oneyama, Chitose

• Tanaka, Masakazu

• Sasaki, Yuichi

• Kanou, Takashi

• Lee, Young-Ho

• Yokogawa, Daisuke

• Dobenecker, Marc-Werner

• Nakagawa, Atushi

• Okada, Masato

• Ikegami, Takahisa

抄録

This research was originally published in Journal of Biological Chemistry. Hiroaki Tanaka, Ken-ichi Akagi, Chitose Oneyama, Masakazu Tanaka, Yuichi Sasaki, Takashi Kanou, Young-Ho Lee, Daisuke Yokogawa, Marc-Werner Dobenecker, Atsushi Nakagawa, Masato Okada and Takahisa Ikegami. Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains. Journal of Biological Chemistry. 2013; 288, 15240-15254. © the American Society for Biochemistry and Molecular Biology.

Proteins with Src homology 2 (SH2) domains play major roles in tyrosine kinase signaling. Structures of many SH2 domains have been studied, and the regions involved in their interactions with ligands have been elucidated. However, these analyses have been performed using short peptides consisting of phosphotyrosine followed by a few amino acids, which are described as the canonical recognition sites. Here, we report the solution structure of the SH2 domain of C-terminal Src kinase (Csk) in complex with a longer phosphopeptide from the Csk-binding protein (Cbp). This structure, together with biochemical experiments, revealed the existence of a novel binding region in addition to the canonical phosphotyrosine 314-binding site of Cbp. Mutational analysis of this second region in cells showed that both canonical and novel binding sites are required for tumor suppression through the Cbp-Csk interaction. Furthermore, the data indicate an allosteric connection between Cbp binding and Csk activation that arises from residues in the βB/βCloop of the SH2 domain.

収録刊行物

• Journal of Biological Chemistry

  Journal of Biological Chemistry 288 (21), 15240-15254, 2013-05

  American Society for Biochemistry and Molecular Biology

詳細情報

• CRID: 1050299693925400576
• NII論文ID: 120006770869
• NII書誌ID: AA1202441X
• ISSN: 1083351X
• HANDLE: 11094/73661
• 本文言語コード: en
• 資料種別: journal article
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