A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H

Satoshi Ohte, Masashi Shin, Hiroki Sasanuma, Katsumi Yoneyama, Masumi Akita, Kenji Ikebuchi, Eijiro Jimi, Yuichi Maruki, Masaru Matsuoka, Akira Namba, Hiroshi Tomoda, Yasushi Okazaki, Akira Ohtake, Hiromi Oda, Ichiro Owan, Tetsuya Yoda, Hirokazu Furuya, Jyunji Kamizono, Hiroshi Kitoh, Yasuharu NakashimaTakafumi Susami, Nobuhiko Haga, Tetsuo Komori, Takenobu Katagiri

研究成果: Contribution to journalArticle査読

35 被引用数 (Scopus)

抄録

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. Constitutively activated mutants of a bone morphogenetic protein (BMP) receptor, ALK2, have been identified in patients with FOP. Recently, a novel ALK2 mutation, L196P, was found in the most benign case of FOP reported thus far. In the present study, we examined the biological activities of ALK2(L196P) in vitro. Over-expression of ALK2(L196P) induced BMP-specific activities, including the suppression of myogenesis, the induction of alkaline phosphatase activity, increased BMP-specific luciferase reporter activity, and increased phosphorylation of Smad1/5 but not Erk1/2 or p38. The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP. ALK2(L196P) was equally or more resistant to inhibitors in comparison to ALK2(R206H). These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in patients with this mutation.

本文言語英語
ページ(範囲)213-218
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
407
1
DOI
出版ステータス出版済み - 4 1 2011

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

フィンガープリント

「A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル