A novel, secreted form of human ADAM 12 (meltrin α) provokes myogenesis in vivo
A novel, secreted form of human ADAM 12 (meltrin α) provokes myogenesis in vivo
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DOI：
10.1074/jbc.273.1.157
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发表时间：
1998-01-02
影响因子：
4.8
通讯作者：
Wewer, UM
中科院分区：
文献类型：
--
作者：
Gilpin, BJ;Loechel, F;Wewer, UM
细胞表面蛋白的Adam（崩解蛋白和金属蛋白酶）家族可能在细胞相互作用和调节细胞反应中具有重要作用，在本报告中，我们描述了一种新颖的，分泌的人Adam 12（Meltrin Alpha），指定为Adam 12 -s（简称为s）和较大的膜结合形式，称为Adam 12-L（长形式为L）。这两种形式是通过位于染色体10q26上的单个基因的替代剪接而产生的。 Northern印迹表明，两种形式的mRNA在人类术语中都很丰富，并且在某些肿瘤细胞系中也存在。在正常的人类成人骨骼，心脏和平滑肌中，也可以检测到Adam 12-L转录本。不区分肌肉细胞且未表达任何形式的亚当12的人A204胚胎横纹肌肉瘤细胞稳定地用Adam 12-s小微生本编码崩溃蛋白结构域，富含半胱氨酸的结构域，以及独特的34氨基酸羧基终端。源自这些转染细胞的裸小鼠肿瘤包含明显小鼠起源的异位肌肉细胞，如物种特异性标记所示。这些结果可能在肌肉定向基因和细胞疗法的发展中具有潜在的应用。
The ADAM (A Disintegrin And Metalloprotease) family of cell-surface proteins may have an important role in cellular interactions and in modulating cellular responses, In this report we describe a novel, secreted form of human ADAM 12 (meltrin alpha), designated ADAM 12-S (S for short), and a larger, membrane-bound form designated ADAM 12-L (L for long form). These two forms arise by alternative splicing of a single gene located on chromosome 10q26. Northern blotting demonstrated that mRNAs of both forms are abundant in human term placenta and are also present in some tumor cell lines. The ADAM 12-L transcript can also be detected in normal human adult skeletal, cardiac, and smooth muscle. Human A204 embryonal rhabdomyosarcoma cells that do not differentiate into muscle cells and do not express any form of ADAM 12 were stably transfected with an ADAM 12-S minigene encoding the disintegrin domain, the cysteine-rich domain, and the unique 34 amino acid carboxyl terminus. Nude mouse tumors derived from these transfected cells contained ectopic muscle cells of apparent mouse origin as shown by species-specific markers. These results may have potential applications in the development of muscle-directed gene and cell therapies.