Mechanism of Ret activation by a mutation at aspartic acid 631 identified in sporadic pheochromocytoma

Naoya Asai, Toshihide Iwashita, Hideki Murakami, Hiroki Takanari, Kenji Ohmori, Masatoshi Ichihara, Masahide Takahashi

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11 Citations (Scopus)


Mutations at aspartic acid 631 in Ret were reported in sporadic pheochromocytoma and medullary thyroid carcinoma. We replaced this aspartic acid with four other amino acids including tyrosine, glycine, asparagine, and alanine and investigated the transforming activity of these mutant cDNAs. Among them, RET cDNA with a mutation of aspartic acid to tyrosine (D631Y) that was reported in sporadic pheochromocytoma showed high transforming activity. The D631Y mutation activated Ret by inducing its disulfide-linked dimerization in the transfectant as observed for multiple endocrine neoplasia (MEN) 2A mutations at cysteine 609, 611, 618, 620, 630, or 634. Further mutation analysis suggested that cysteine 630 or 634 could be involved in the disulfide-linked Ret dimerization induced by the D631Y mutation.

Original languageEnglish
Pages (from-to)587-590
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 24-02-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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