Activin receptor type-1

Definition:

Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B. Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity).

References:

[1]. M Macías-Silva, et al. Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem. 1998 Oct 2;273(40):25628-36. [Content Brief]

[2]. Nina Renlund, et al. Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor. J Endocrinol. 2007 Oct;195(1):95-103. [Content Brief]

[3]. Mai Fujimoto, et al. Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors. Mol Endocrinol. 2015 Jan;29(1):140-52. [Content Brief]

[4]. Apirat Chaikuad, et al. Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem. 2012 Oct 26;287(44):36990-8. [Content Brief]

[5]. Jinyong Luo, et al. TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells. J Biol Chem. 2010 Sep 17;285(38):29588-98. [Content Brief]

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