ALK-1 蛋白, Cynomolgus (HEK293, His)

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, Cynomolgus (HEK293, His) is produced in HEK293 cells with a C-Terminal His-tag. It consists of 118 amino acids (D22-Q118).

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 human ALK-1 (5 μg/mL; preincubated for 3 minutes) abolishes Hey1, Hey2 and Id2 genes induction by serum in primary human endothelial cells^[4].

Measured by its ability to inhibit BMP-9-induced alkaline phosphatase production by ATDC5 mouse chondrogenic cells. The ED₅₀ for this effect is 3.992 ng/mL in the presence of 2 ng/mL of rhBMP-9, corresponding to a specific activity is 2.505×10⁵ U/mg.

• 
  Measured by its ability to inhibit BMP-9-induced alkaline phosphatase production by ATDC5 mouse chondrogenic cells. The ED₅₀ for this effect is 3.992 ng/mL in the presence of 2 ng/mL of rhBMP-9, corresponding to a specific activity is 2.505×10⁵ U/mg.

Cynomolgus

HEK293

C-His

XP_005570958 (D22-Q118)

102143641  [NCBI]

DPVKPSRGPLVTCTCESPHCRGPTCQGAWCTVVLVREEGRHPQEHRGCGNLHRELCRGRPTEFVNHYCCDSHLCNRNVSLVLEATQTPSEQPGTDSQ

Approximately 21-25 kDa due to the glycosylation.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [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]. Kerstin Wöltje, et al. Serum induces transcription of Hey1 and Hey2 genes by Alk1 but not Notch signaling in endothelial cells. PLoS One. 2015 Mar 23;10(3):e0120547.  [Content Brief]