Liu Yunshan, Hair Gregory A, Boden Scott D, Viggeswarapu Manjula, Titus Louisa
Department of Orthopaedic Surgery, Emory University School of Medicine, Decatur, Georgia, USA.
J Bone Miner Res. 2002 Mar;17(3):406-14. doi: 10.1359/jbmr.2002.17.3.406.
Rat LIM mineralization protein 1 (LMP-1, an LIM domain protein) mediates bone morphogenetic protein 6 (BMP-6) induction of bone nodule formation in fetal rat calvarial osteoblast (ROB) cultures. We have isolated the complementary DNA (cDNA) for the human homologue of LMP-1 from an adult human heart cDNA library and showed that when overexpressed it is osteoinductive in the same culture system. The recently revised cDNA sequence of Enigma, the protein product of which binds to the insulin receptor and the tyrosine kinase receptor ret, now matches the nucleotide sequence of human LMP-1 (hLMP-1). A truncated, 223 amino acid (AA) LMP-1(t) protein has identical effects as the full-length protein, despite the deletion of the LIM domains. Two splice variants of human LMP-1 have been detected. Human LMP-2 has a 119-base pair (bp) deletion between bp 325 and 444 and a 17-bp insertion at bp 444. The resulting derived protein contains 423 AA with the LIM domains intact and does not induce bone formation when overexpressed in ROB cultures. Human LMP-3 has the same 17 nucleotide insertion at bp 444, resulting in a shift in the reading frame that causes a stop codon to occur at bp 505-507. The resulting 153 AA protein does not have the LIM domains, but overexpression of hLMP-3 induces bone formation in osteoblast cultures. These findings suggest that the LIM domains are not required for LMPs to induce bone formation. In addition, a small region (36 AA) of the LMP-1 protein may be required for bone formation.
大鼠LIM矿化蛋白1（LMP-1，一种含LIM结构域的蛋白）在胎鼠颅骨成骨细胞（ROB）培养物中介导骨形态发生蛋白6（BMP-6）诱导骨结节形成。我们从成人心脏cDNA文库中分离出了LMP-1人类同源物的互补DNA（cDNA），并表明在同一培养系统中过表达时它具有骨诱导性。最近修订的Enigma的cDNA序列，其蛋白产物与胰岛素受体和酪氨酸激酶受体ret结合，现在与人类LMP-1（hLMP-1）的核苷酸序列匹配。尽管缺失了LIM结构域，但截短的223个氨基酸（AA）的LMP-1（t）蛋白与全长蛋白具有相同的作用。已检测到人类LMP-1的两种剪接变体。人类LMP-2在第325至444碱基对（bp）之间有119碱基对（bp）的缺失，在第444碱基对处有17碱基对的插入。所得的衍生蛋白含有423个氨基酸，LIM结构域完整，在ROB培养物中过表达时不诱导骨形成。人类LMP-3在第444碱基对处有相同的17个核苷酸插入，导致阅读框移位，从而在第505 - 507碱基对处出现终止密码子。所得的153个氨基酸的蛋白没有LIM结构域，但hLMP-3的过表达在成骨细胞培养物中诱导骨形成。这些发现表明，LIM结构域对于LMPs诱导骨形成并非必需。此外，LMP-1蛋白的一个小区域（36个氨基酸）可能是骨形成所必需的。
