ALK-7

ALK-7, also known as ACVR1C, is a type I receptor serine-threonine kinase mediate inhibitory as well as stimulatory signals for growth and differentiation by binding to members of the TGF-β superfamily. ALK-7 combined with specific ligands, such as Nodal, activin B and growth differentiation factor (GDF), can activate Smads and other signaling pathways, thereby regulating cell proliferation, differentiation and apoptosis in various cells. ALK-7 is predominantly expressed in central nervous system. ALK-7 can form complexes with type II receptor serine-threonine kinases for TGF-β and activin in a ligand-dependent manner^[1].
The ALK-7 gene encodes a 55-kDa cell-surface protein that exhibits up to 78% amino acid sequence identity in the kinase domain to previously isolated type I receptors for TGF-β and activin. In the extracellular domain, however, ALK-7 is more divergent, displaying comparable similarities with all members of the ALK subfamily. Originally identified and cloned from rat brain, ALK-7 mRNA is present throughout the digestive and central nervous system of rats. The function of ALK-7 as a type I receptor was confirmed with a constitutively activemutant form that activated a TGF-β/activin response reporter. ALK-7 has also been found to activate some components of the Smad pathway, such as Smad2 and Smad3, in fetal and adult rat pancreas. In the rat pheochromocytoma PC12 cell line, ALK-7 not only activated both Smad2, Smad3, and the MAPK of extracellular signal-regulated kinase and JNK, but it inhibits cell proliferation as well. The human gene for ALK-7 has been mapped to the genetic location of 2q24.1-q3, with most of the mRNA located in the brain, pancreas, and colon. ALK-7 mediates high-ambient glucose-induced cardiomyoblasts apoptosis through the activation of Smad2/3^[1][2][3].