BMP Type II Receptor (BMPR2)  (骨形态发生蛋白 II 型受体)

骨形态发生蛋白 II 型受体 (BMPR2) 是跨膜丝氨酸/苏氨酸激酶骨形态发生蛋白 (BMP) 受体家族的一员。BMP 参与软骨内骨形成和胚胎发生，通过两种 BMP 受体异质复合物的形成传递信号：I 型受体 (50-55 KD) 和 II 型受体 (70-80 KD)。II 型受体磷酸化并激活自磷酸化的 I 型受体，然后结合并激活 SMAD 转录调控因子^[1][2]。骨形态发生蛋白 II 型受体在心脏和肝脏中高度表达，参与成骨和细胞分化，对胚胎发生、发育和成体组织稳态至关重要。骨形态发生蛋白 II 型受体的 BMPR2通路可抑制肺循环内平滑肌细胞 (SMC) 增殖，尤其是在肺小动脉内。突变的 BMPR2 与发生肺动脉高压 (PAH) 增加的易感性相关^[1]。骨形态发生蛋白 II 型受体是微管蛋白稳定所必需的，因为最近的研究表明，骨形态发生蛋白 II 型受体调节癌细胞中独立于 BMP I 型受体 (BMPR1) 或 Smad-1/5 转录因子的细胞存活信号。骨形态发生蛋白 II 型受体转运蛋白的突变导致 BMP 信号过度活跃，导致微管不稳定的神经疾病。抑制骨形态发生蛋白 II 型受体 BMPR2 使微管不稳定，会导致溶酶体激活，促进癌细胞的细胞死亡进程^[3]。特别是 BMPR2 启动子 DNA 甲基化与瓣膜性心脏病 (VHD) 的严重程度有很强的相关性，这使得 BMPR2 可以作为瓣膜性心脏病 (VHD) 的良好生物标志物。同时，DNA 甲基化可能通过调节 BMP 信号和增加细胞凋亡而引起多环芳烃化^[4]。骨形态发生蛋白 II 型受体的蛋白序列在不同物种间的序列差异保守性较高，人与大鼠、小鼠间的序列相似度分别为 96.15% 和 96.63%。

BMP Type II Receptor (BMPR2) is a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. BMPs are involved in endochondral bone formation and embryogenesis, transducing signals through the formation of heteromeric complexes of 2 types BMP receptors: type I receptors (50-55 kD) and type II receptors (70-80 kD). Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators^[1][2]. BMPR2 is highly expressed in the heart and liver, and involves in osteogenesis and cell differentiation, essential for embryogenesis, development, and adult tissue homeostasis. The BMPR2 pathway inhibits smooth muscle cell (SMC) proliferation within the pulmonary circulation, primarily within the small pulmonary arterioles. When mutated, BMPR2 is associated with an increased susceptibility to develop pulmonary arterial hypertension (PAH)^[1]. BMPR2 is essential for tubulin stability, as recent studies have shown that BMP2 regulates cell survival signaling events in cancer cells independent of the BMP type 1 receptor (BMPR1) or the Smad-1/5 transcription factor. Mutations in BMPR2 trafficking proteins leads to overactive BMP signaling, which leads to neurological diseases caused by BMPR2 stabilization of the microtubules. Inhibition of BMPR2 destabilizes the microtubules, thus leads to lysosomes activation in promoting cell death progress of cancer cells^[3]. Particularly, there is strong correlation between BMPR2 promoter DNA methylation and the severity of valvular heart disease (VHD), which makes BMPR2 serve as good biomarkers of VHD. Meanwhile, DNA methylation may cause PAH through deregulation of BMP signaling and increased apoptosis^[4]. The sequences of BMPR2 protein are conserved among different species, and the sequence of human shares a high similarity with rat (96.15%) and mouse (96.63%), respectively.

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