PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif
PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif
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DOI：
10.1016/j.bbrc.2008.03.158
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发表时间：
2008-06-27
影响因子：
3.1
通讯作者：
Murakami, S.
中科院分区：
文献类型：
--
作者：
Tomoeda, M.;Yamada, S.;Murakami, S.
我们以前确定了新的基因，牙周韧带相关蛋白-1（PLAP-1）/asporin和报告，PLAP-1/asporin抑制骨形态发生蛋白-2（BMP-2）诱导的牙周韧带（PDL）细胞的细胞分化可能是通过与BMP-2的直接相互作用。在这里，我们阐明了该蛋白对BMP-2诱导的PDL细胞分化的详细调控机制。重组PLAP-1 /asporin抑制BMP-2诱导的PDL细胞分化，并竞争性地阻止BMP-2与BMP受体-IB（BMPR-IB）结合，从而抑制BMP依赖的Smad蛋白的活化。在PLAP-1 /asporin中诱导富含亮氨酸重复序列（LRR）基序突变，尤其是LRR 5，挽救了PLAP-1/asporin对BMP-2的抑制作用。相比之下，PLAP-1/asporin LRR 5序列中的26个氨基酸的肽抑制BMP-2活性。我们的研究结果表明，PLAP-1 /asporin抑制BMP-2诱导的PDL细胞分化的BMP-2信号通路的失活，LRR，特别是LRR 5的PLAP-1 /asporin，在PLAP-1/asporin-BMP-2的相互作用中发挥重要作用。(C)2008年爱思唯尔公司All rights reserved.
We previously identified the novel gene, periodontal ligament-associated protein-1 (PLAP-1)/asporin and reported that PLAP-1/asporin inhibited bone morphogenetic protein-2 (BMP-2)-induced cytodifferentiation of periodontal ligament (PDL) cells probably by direct interaction with BMP-2. Here, we elucidated the detailed regulatory mechanism of this protein on BMP-2-induced cytodifferentiation of PDL cells. Recombinant PLAP-1 /asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins. The induction of mutation to the leucine-rich repeat (LRR) motif, especially LRR5, within PLAP-1 /asporin rescued the inhibitory effect of PLAP-I /asporin on BMP-2. By contrast, a 26-amino acid peptide in the PLAP-1/asporin LRR5 sequence inhibited BMP-2 activity. Our findings indicate that PLAP-1 /asporin inhibits BMP-2-induced differentiation of PDL cells resulting from inactivation of the BMP-2 signaling pathway and that LRR, especially LRR5 of PLAP-1 /asporin, plays an important role in the PLAP-1/asporin-BMP-2 interaction. (C) 2008 Elsevier Inc. All rights reserved.