A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor - PubMed (original) (raw)
. 2008 Dec 19;377(3):905-9.
doi: 10.1016/j.bbrc.2008.10.093. Epub 2008 Oct 24.
Kazuhiro Kanomata, Junya Nojima, Shoichiro Kokabu, Masumi Akita, Kenji Ikebuchi, Eijiro Jimi, Tetsuo Komori, Yuichi Maruki, Masaru Matsuoka, Kohei Miyazono, Konosuke Nakayama, Akira Nanba, Hiroshi Tomoda, Yasushi Okazaki, Akira Ohtake, Hiromi Oda, Ichiro Owan, Tetsuya Yoda, Nobuhiko Haga, Hirokazu Furuya, Takenobu Katagiri
Affiliations
- PMID: 18952055
- DOI: 10.1016/j.bbrc.2008.10.093
A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor
Toru Fukuda et al. Biochem Biophys Res Commun. 2008.
Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic bone formation in muscle tissues. A common mutation among FOP patients has been identified in ALK2, ALK2(R206H), which encodes a constitutively active bone morphogenetic protein (BMP) receptor. Recently, a unique mutation of ALK2, ALK2(G356D), was identified to be a novel mutation in a Japanese FOP patient who had unique clinical features. Over-expression of ALK2(G356D) induced phosphorylation of Smad1/5/8 and activated Id1-luc and alkaline phosphatase activity in myoblasts. However, the over-expression failed to activate phosphorylation of p38, ERK1/2, and CAGA-luc activity. These ALK2(G356D) activities were weaker than those of ALK2(R206H), and they were suppressed by a specific inhibitor of the BMP-regulated Smad pathway. These findings suggest that ALK2(G356D) induces heterotopic bone formation via activation of a BMP-regulated Smad pathway. The quantitative difference between ALK2(G356D) and ALK2(R206H) activities may have caused the phenotypic differences in these patients.
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