Authors: Senga, Takeshi; Hasegawa, Hitoki; Tanaka, Miwa; Rahman, Mohammad Aminur; Ito, Satoko; Hamaguchi, Michinari

Source: Cancer Science, Volume 99, Number 3, March 2008 , pp. 571-575(5)

Publisher: Wiley-Blackwell

Abstract:

We have previously reported that c-Src is activated by mercuric chloride (HgCl₂). We investigated the mechanism of this activation and found that in vitro activation of c-Src by HgCl₂ did not require tyrosine residues at 416 and 527. Both SH2 and SH3 domains of c-Src were dispensable for the activation by HgCl₂. In contrast, iodoacetoamide (IAA) that binds to thiol side chain of cysteine blocked the activation of c-Src by HgCl₂. To obtain more clues, each cysteine residue of c-Src was replaced with alanine. Of six cysteine residues in the kinase domain of c-Src, Cys483 and Cys498 located in the C-terminal portion as a cysteine-cluster (CC) motif were critical for the activation. In addition, other Src family kinases, Yes and Lyn, were activated by treatment with HgCl₂, and cysteine residues, especially those correspond to Cys498 of Src in the CC motif of these kinases, were also required for the activation of the kinases by HgCl₂. In addition to these observations, treatment of cells with HgCl₂ dramatically activated the wild-type c-Src, whereas it could not activate the mutant form of Src with a substitution of Cys498. Taken together, our results disclose that cysteine residues in the CC motif of c-Src, Cys483 and Cys498, act as a module for the activation of the kinase by a heavy metal compound, mercuric chloride. (Cancer Sci 2008; 99: 571-575)

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1349-7006.2007.00714.x

Publication date: 2008-03-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Oncology
• By this author: Senga, Takeshi ;  Hasegawa, Hitoki ;  Tanaka, Miwa ;  Rahman, Mohammad Aminur ;  Ito, Satoko ;  Hamaguchi, Michinari

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers