ALK-1 蛋白, Rat (HEK293, His-Fc)

ALK-1, also known as ACVRL1, is a type I receptor for TGF-β superfamily with 2 ligands, BMP9 and BMP10. ALK-1 is predominantly expressed in endothelial cells and plays a critical role in regulating developmental and pathological angiogenesis^[1][2]. ALK-1 Protein, Rat (HEK293, His-Fc) is produced in HEK293 cells with a C-Terminal His-tag and a C-Terminal Fc-tag.

ALK-1，也称为 ACVRL1，是 TGF-β 超家族的 I 型受体，具有 2 个配体：BMP9 和 BMP10。ALK-1 主要在内皮细胞中表达，在调节血管生成中发挥关键作用^[1][2]。成熟人类 ALK-1 占比 89% 与小鼠和大鼠 ALK-1 的氨基酸序列相同。而小鼠 ALK-1 与大鼠 ALK-1 蛋白具有 96% 的氨基酸序列同一性。在 TβR-II 或激活素 II 型受体存在的情况下，ALK-1 能够与 TGF-β1 或激活素结合，分别。然而，ALK-1 不会引起特定的转录反应。因此，ALK-1 被认为是一种“孤儿”受体。ALK-1 是一种 I 型受体，介导 BMP9（骨形态发生蛋白）和 BMP10（TGF-β 超家族蛋白）的信号传导。通过 ALK-1 的信号传导导致细胞内 Smad 1/5/8 级联的磷酸化，从而激活促血管生成转录因子，例如 ID1 和 ID3。ALK-1 与 TGF-β1 结合并使 Smad1 和 Smad5 磷酸化。HepG2 细胞中 ALK-1 的过度表达会抑制 ALK5 介导的 TGF-β1 反应。ALK-1 和 ALK5 之间的平衡可能对于控制血管生成过程中内皮的特性至关重要^[1]。BMP9/BMP10/ALK-1 信号传导通过 Smad4 依赖性途径控制特定基因表达程序和 Kupffer 细胞 (KC) 的存活。从功能上来说，ALK-1 的缺失导致 L 的捕获受损和单核细胞增多症，以及大量播散性感染^[2]。ALK-1 在胚胎发生和成体阶段在血管中表达。此外，ALK-1 基因突变与 II 型遗传性出血性毛细血管扩张症有关^[1]。ALK-1 抑制人脐静脉内皮细胞中 BMP9 介导的 Id-1 表达。在鸡绒毛尿囊膜测定中，ALK-1 减少 VEGF、FGF 和 BMP10 介导的血管形成。此外，ALK1 还可减轻接受 MCF7 乳腺癌细胞原位移植的小鼠的肿瘤负荷^[3]。

Recombinant mouse ALK-1 (25 ng/mL and 1 μg/mL; for 4 days) competitively binds ALK1 ligands, significantly inhibits BMP-9 (5 ng/mL) induced alkaline phosphatase (ALP) activity and markedly reduces the pro-calcificatory actions of BMP-9 on primary murine vascular smooth muscle cells (VSMC)^[4].

Recombinant mouse ALK-1 (3 mg/kg; twice weekly for 7 weeks) treatment reduces tumor burden in athymic nude mice receiving orthotopic grafts of MCF7 mammary adenocarcinoma cells^[3].

Rat

HEK293

C-hFc;C-His

P80203 (D23-A118)

25237  [NCBI]

DLVKPSRGQLVNCTCENPHCKRPICQGAWCTVVLVREQGRHPQVYRGCGSLNQELCLGRPTEFVNHHCCYRSFCNHNVSLMLEATQTPSEEPEVDA

50-55 kDa

Greater than 90% as determined by reducing SDS-PAGE

<1 EU/μg, determined by LAL method.

• [1]. S P Oh, et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2626-31.  [Content Brief]

  [2]. Dianyuan Zhao, et al. ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection. J Clin Invest. 2022 Feb 1;132(3):e150489.  [Content Brief]

  [3]. Dianne Mitchell, et al. ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth. Mol Cancer Ther. 2010 Feb;9(2):379-88.  [Content Brief]

  [4]. Dongxing Zhu, et al. BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway. J Cell Mol Med. 2015 Jan;19(1):165-74.  [Content Brief]