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

被引：10

作者：

Asai, N ^{[1
]}

Iwashita, T ^{[1
]}

Murakami, H ^{[1
]}

Takanari, H ^{[1
]}

Ohmori, K ^{[1
]}

Ichihara, M ^{[1
]}

Takahashi, M ^{[1
]}

机构：

[1] Nagoya Univ, Sch Med, Dept Pathol, Showa Ku, Nagoya, Aichi 4668550, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1999年 / 255卷 / 03期

关键词：

D O I：

10.1006/bbrc.1999.0237

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 1999 Academic Press.

引用

页码：587 / 590

页数：4

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