ALK5 Extracellular Domain (human, recombinant)

Activin receptor-like kinase 5 (ALK5), also known as TGF-β receptor type 1 (TGF-βRI), is a type I transmembrane glycoprotein, serine/threonine kinase, and member of the TGF-β superfamily that is ubiquitously expressed.^1,2 It is composed of an extracellular ligand-binding domain, a single transmembrane domain, an intracellular serine/threonine kinase domain, and a cytoplasmic serine/threonine-rich region.¹ The ALK5 ligand TGF-β mediates the formation of a complex that includes ALK5 and the type II transmembrane glycoprotein TGF-βRII, which phosphorylates ALK5 to induce intracellular signaling and phosphorylation of SMAD2 and SMAD3 to regulate gene expression.^1,3 The ligands myostatin and growth differentiation factor 11 (GDF-11) induce formation of a complex between ALK5, TGF-βRI, activin receptor type 2A (ACTRIIA), and ACTRIIB to activate SMAD signaling in a similar manner. ALK5 signaling has roles in endothelial cell proliferation and migration, as well as angiogenesis.^4,2 Mutations in TGFBR1 are associated with Loeys-Dietz syndrome, which is a connective tissue disorder characterized by a variety of mild-to-severe vascular defects, including aortic aneurysm.⁵ Cayman’s ALK5 Extracellular Domain (human, recombinant) protein can be used for binding assays. This protein is a disulfide-linked homodimer. The reduced monomer, composed of ALK5 (amino acids 34-125) fused to His-tagged human IgG1 Fc at its C-terminus, consists of 340 amino acids, has a calculated molecular weight of 38.1 kDa, and a predicted N-terminus of Leu34 after signal peptide cleavage. As a result of glycosylation, the monomer migrates at approximately 45-50 kDa by SDS-PAGE under reducing conditions.

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1. Tsuchida, K., Nakatani, M., Uezumi, A., et al. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr. J. 55(1), 11-21 (2008).

2. van Meeteren, L.A., and ten Dijke, P. Regulation of endothelial cell plasticity by TGF-β. Cell Tissue Res. 347(1), 177-186 (2012).

3. Nickel, J., ten Dijke, P., and Mueller, T.D. TGF-β family co-receptor function and signaling. Acta Biochim. Biophys. Sin. (Shanghai) 50(1), 12-36 (2018).

4. Goumans, M.-J., Valdimarsdottir, G., Itoh, S., et al. Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J. 21(7), 1743-1753 (2002).

5. Gallo, E.M., Loch, D.C., Habashi, J.P., et al. Angiotensin II-dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis. J. Clin. Invest. 124(1), 448-460 (2014).