Human ALK-1 Antibody

Transforming Growth Factor beta (TGF-beta) superfamily ligands exert their biological activities via binding to heteromeric receptor complexes of two types (I and II) of serine/threonine kinases. Type II receptors are constitutively active kinases that phosphorylate type I receptors upon ligand binding. In turn, activated type I kinases phosphorylate downstream signaling molecules including the various smads. Transmembrane proteoglycans, including the type III receptor (betaglycan) and endoglin, can bind and present some of the TGF-beta superfamily ligands to type I and II receptor complexes and enhance their cellular responses. Seven type I receptors (also termed activin receptor-like kinase (ALK)) and five type II receptors have been isolated from mammals. ALK-2, -3, -4, -5, and -6 are also known as Activin R1A, BMPR-1A, Activin R1B, TGF-beta R1, and BMPR-1B, respectively, reflecting their ligand preferences. Evidence suggests that TGF-beta 1, TGF-beta 3 and an unknown ligand present in serum can activate chimeric ALK-1. ALK-1 shares with other type I receptors a cysteine-rich domain with conserved cysteine spacing in the extracellular region, and a glycine- and serine-rich domain (the GS domain) preceding the kinase domain. ALK-1 is expressed highly in endothelial cells and other highly vascularized tissues. The expression patterns of ALK-1 parallels that of endoglin. Mutations in ALK-1 as well as in endoglin are associated with hereditary hemorrhagic telangiectasia (HHT), suggesting a critical role for ALK-1 in the control of blood vessel development or repair. Human and mouse ALK-1 share approximately 71% amino acid sequence identity in their extracellular regions.