ALK-6  (骨形态发生蛋白 1B 型受体)

骨形态发生蛋白 1B 型受体，也被称为 CDw293 (分化簇 w293)，是跨膜丝氨酸/苏氨酸激酶骨形态发生蛋白 (BMP) 受体家族的成员。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，包括 I 型受体 (50-55kd) 和 II 型受体 (70-80kd)。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]。骨形态发生蛋白 1B 型受体是 BMP-7 (或 OP-1) 和 GDF-5 的受体，通过与 GDF-5 相互作用正向调节软骨细胞分化^[2]。骨形态发生蛋白 1B 型受体信号也由 SCUBE3 (BMP-2 和 BMP-4的共受体) 控制，将 BMP 受体复合物引入筏微域，并可能通过增强 BMP 和 BMP I 型受体之间的特异性互作来正反馈调节信号^[3]。骨形态发生蛋白 1B 型受体通过调节 BMP 信号参与控制生长、形态发生以及骨和牙齿的发育，在体内对软骨形成至关重要，而另一种相近的 I 型受体 BMPR1A (或 ALK-3) 和 骨形态发生蛋白 1B 型受体在早期软骨形成中有功能冗余^[4]。ALK-6/GDF-9/BMP-15 信号在山羊增殖过程中起着关键作用。骨形态发生蛋白 1B 型受体和 GDF-9 在 20 个组织中广泛表达，在卵巢中表达最高，而 BMP-15 基因仅在卵巢和垂体中表达^[5]。骨形态发生蛋白 1B 型受体在不同物种间的序列差异保守性高，人与大鼠、小鼠间的序列相似度分别为 98.21% 和 98.21%。

ALK-6, also known as CDw293 (cluster of differentiation w293), 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]. ALK-6 is the receptor for BMP-7/OP-1 and GDF-5, positively regulates chondrocyte differentiation through GDF-5 interaction^[2]. ALK-6 signaling is also controlled by SCUBE3, a BMP-2/BMP-4 co-receptor, recruits the BMP receptor complexes into raft microdomains, and positively modulates signaling possibly by augmenting the specific interactions between BMPs and BMP type I receptors^[3]. ALK-6 involves in controlling growth, morphogenesis, and bone and teeth development through modulation of BMP signaling, is essential for chondrogenesis in vivo, while BMPR1A/ALK-3 and ALK-6 have overlapping functions during early chondrogenesis^[4]. ALK-6/GDF-9/BMP-15 signals play a key role in prolificacy. ALK-6 and GDF-9 are widely expressed in 20 tissues with highest in ovary, while BMP-15 gene was expressed exclusively in ovary and pituitary^[5]. The sequences of ALK-6 are highly conserved among different species, and the sequence of human shares a high similarity with rat (98.21%) and mouse (98.21%), respectively.

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