ACVRL1/ALK1 Protein, Mouse (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]. ACVRL1/ALK1 Protein, Mouse (HEK293, His-Fc) is produced in HEK293 cells with a C-Terminal His-tag and a C-Terminal Fc-tag. It consists of 119 amino acids (M1-P119).

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 angiogenesis^[1][2].
Mature human ALK-1 shares 89% amino acid sequence identity with mouse and rat ALK-1. While, mouse ALK-1 shares 96% aa sequence identity with rat ALK-1 protein.
ALK-1 is able to bind to TGF-β1 or activins in the presence of either TβR-II or activin type II receptors, respectively. However, ALK-1 does not elicit a specific transcriptional response. Thus, ALK-1 has been considered an “orphan” receptor. ALK-1 is a type I receptor that mediates signaling of BMP9 (bone morphogenetic protein) and BMP10, proteins in the TGF-β superfamily. Signaling through ALK-1 results in phosphorylation of the intracellular Smad 1/5/8 cascade which activates proangiogenic transcription factors such as ID1 and ID3. ALK-1 binds to TGF-β1 and phosphorylates Smad1 and Smad5. Overexpression of ALK-1 in HepG2 cells inhibits the ALK5-mediated TGF-β1 response. The balance between ALK-1 and ALK5 may be crucial for controlling the properties of endothelium during angiogenesis^[1]. BMP9/BMP10/ALK-1 signaling controlled the specific gene expression program and survival of Kupffer cells (KCs) through a Smad4-dependent pathway. Functionally, the loss of ALK-1 resulted in impaired capture of L. monocytogenes and overwhelming disseminated infections^[2].
ALK-1 is expressed in blood vessels during embryogenesis and adult stages. In addition, mutations of the ALK-1 gene have been linked to the type II hereditary hemorrhagic telangiectasia^[1]. ALK-1 inhibits BMP9-mediated Id-1 expression in human umbilical vein endothelial cells. In a chick chorioallantoic membrane assay, ALK-1 reduces VEGF-, FGF-, and BMP10-mediated vessel formation. In addition, ALK1 reduces tumor burden in mice receiving orthotopic grafts of MCF7 mammary adenocarcinoma cells^[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].

Mouse

HEK293

C-hFc;C-His

Q61288 (M1-P119)

11482  [NCBI]

MTLGSFRRGLLMLSVAFGLTRGDLAKPSKLVNCTCESPHCKRPFCQGSWCTVVLVREQGRHPQVYRGCGSLNQELCLGRPTEFLNHHCCYRSFCNHNVSLMLEATQTPSEEPEVDAHLP

50-55 kDa

Greater than 95% 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]