Rodgers B D, Weber G M
Pediatric Endocrinology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Park 211, 21287, Baltimore, MD, USA.
Comp Biochem Physiol B Biochem Mol Biol. 2001 Jun;129(2-3):597-603. doi: 10.1016/s1096-4959(01)00350-5.
Myostatin (MSTN) negatively regulates mammalian skeletal muscle growth and development by inhibiting myoblast proliferation. Mice and cattle possessing mutant MSTN alleles display a 'double muscling' phenotype characterized by extreme skeletal muscle hypertrophy and/or hyperplasia. MSTN orthologues have been previously characterized in 12 vertebrate species, including the white bass Morone chrysops. Presented herein is the identification and characterization of novel cDNA clones from two additional Morone species: saxatilis (striped bass) and americana (white perch), which were obtained by PCR amplification and subsequent TA-cloning. The predicted amino acid sequence of each cDNA clone contains a putative signal sequence, conserved cysteine residues and a RXXR proteolytic processing site. The different Morone proteins were 97-99% identical to each other and approximately 91, 81, 68 and 67% identical to the tilapia, zebrafish, mammalian and avian proteins, respectively. However, the bioactive domains, which lie downstream of each processing site, were considerably more conserved. They were 99-100% identical within the genus and were approximately 99, 95, 88 and 88% identical to the tilapia, zebrafish, mammalian and avian domains, respectively. This high level of sequence conservation among all known MSTN orthologues suggests that the structure/function relationship of each is equally well conserved among vertebrates.
肌肉生长抑制素(MSTN)通过抑制成肌细胞增殖对哺乳动物骨骼肌的生长和发育起负调控作用。携带突变MSTN等位基因的小鼠和牛呈现出“双肌”表型,其特征为骨骼肌极度肥大和/或增生。此前已在包括白鲈(Morone chrysops)在内的12种脊椎动物中鉴定出MSTN直系同源物。本文介绍了从另外两种海鲈属物种:条纹鲈(saxatilis)和美洲鲈(americana,白鲈)中鉴定和表征新的cDNA克隆的过程,这些克隆是通过PCR扩增和随后的TA克隆获得的。每个cDNA克隆的预测氨基酸序列包含一个假定的信号序列、保守的半胱氨酸残基和一个RXXR蛋白水解加工位点。不同的海鲈属蛋白彼此间的同源性为97 - 99%,分别与罗非鱼、斑马鱼、哺乳动物和鸟类的蛋白同源性约为91%、81%、68%和67%。然而,位于每个加工位点下游的生物活性结构域的保守性要高得多。它们在该属内的同源性为99 - 100%,分别与罗非鱼、斑马鱼、哺乳动物和鸟类的结构域同源性约为99%、95%、88%和88%。所有已知MSTN直系同源物之间的这种高度序列保守性表明,它们各自的结构/功能关系在脊椎动物中同样得到了很好的保守。