Activin receptor type-2B–Activin receptor-like kinase 7 heteromeric receptor complex (ActRIIB–ALK7 complex)

The ActRIIB–ALK7 heteromeric receptor complex is a specialized signaling assembly within the transforming growth factor-beta (TGF-β) superfamily, formed by the association of the type II receptor Activin receptor type-2B (ActRIIB) and the type I receptor Activin receptor-like kinase 7 (ALK7, also known as ACVR1C). This complex is a critical mediator for specific ligands including Activin B, Activin C, Activin E, Nodal, and GDF3, which are primarily involved in metabolic regulation and adipose tissue homeostasis [1, 4, 7, 12]. Upon ligand binding, the ActRIIB component phosphorylates ALK7, which subsequently activates the canonical SMAD2/3 intracellular signaling pathway to regulate gene expression related to adipocyte differentiation and the suppression of lipolysis [15, 17, 18]. Because this complex is highly expressed in adipose tissue and its signaling promotes fat storage while inhibiting energy expenditure, it has emerged as a high-priority therapeutic target for treating obesity and type 2 diabetes [3, 15]. Modern drug development strategies utilize "heteromeric ligand traps" (e.g., ActRIIB-ALK7-Fc) to selectively sequester metabolic ligands while avoiding the off-target inhibition of BMP9 and BMP10, which are associated with the vascular side effects seen in earlier, less selective ActRIIB-based therapies [2, 9, 13].

Other names

ACVR2B–ACVR1C complexActRIIB–ACVR1C complexActRIIB–ActRIC complexActivin receptor type IIB–Activin receptor-like kinase 7 complex

Ligand sequestration, Receptor antagonism, Inhibition of SMAD2/3 signaling