Tsang M, Kim R, de Caestecker M P, Kudoh T, Roberts A B, Dawid I B
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Genesis. 2000 Oct;28(2):47-57. doi: 10.1002/1526-968x(200010)28:2<47::aid-gene20>3.0.co;2-s.
Bone morphogenetic proteins (BMP) are members of the TGFbeta superfamily of secreted factors with important regulatory functions during embryogenesis. We have isolated the zebrafish gene, nma, that encodes a protein with high sequence similarity to human NMA and Xenopus Bambi. It is also similar to TGFbeta type I serine/theronine kinase receptors in the extracellular ligand-binding domain but lacks a cytoplasmic kinase domain. During development, nma expression is similar to that of bmp2b and bmp4, and analysis in the dorsalized and ventralized zebrafish mutants swirl and chordino indicates that nma is regulated by BMP signaling. Overexpression of nma during zebrafish and Xenopus development resulted in phenotypes that appear to be based on inhibition of BMP signaling. Biochemically, NMA can associate with TGFbeta type II receptors and bind to TGFbeta ligand. We propose that nma is a BMP-regulated gene whose function is to attenuate BMP signaling during development through interactions with type II receptors and ligands.
骨形态发生蛋白(BMP)是分泌因子TGFβ超家族的成员,在胚胎发育过程中具有重要的调节功能。我们分离出了斑马鱼基因nma,它编码一种与人类NMA和非洲爪蟾Bambi具有高度序列相似性的蛋白质。它在细胞外配体结合结构域也与TGFβ I型丝氨酸/苏氨酸激酶受体相似,但缺乏细胞质激酶结构域。在发育过程中,nma的表达与bmp2b和bmp4相似,对斑马鱼背化和腹化突变体swirl和chordino的分析表明,nma受BMP信号调控。在斑马鱼和非洲爪蟾发育过程中过表达nma会导致一些表型,这些表型似乎是基于对BMP信号的抑制。从生化角度来看,NMA可以与TGFβ II型受体结合,并与TGFβ配体结合。我们提出,nma是一个受BMP调控的基因,其功能是在发育过程中通过与II型受体和配体相互作用来减弱BMP信号。