ALK2

ALK2 (also known as Activin receptor-like kinase 2 or ACVR1) is a protein that in humans is encoded by the ACVR1 gene. It is a type I receptor for the TGF-beta (transforming growth factor-beta) family of growth factors. ALK2 plays a crucial role in cell growth, cell differentiation, and apoptosis (programmed cell death).

Structure

ALK2 is a single-pass type I membrane protein. It is composed of a ligand-binding extracellular domain, a single transmembrane segment, and a cytoplasmic domain with predicted serine/threonine kinase activity.

Function

ALK2 is a receptor for members of the TGF-beta family. Upon ligand binding, ALK2 forms a complex with a type II receptor, which phosphorylates and activates the ALK2 kinase domain. The activated ALK2 then phosphorylates and activates SMAD proteins, which translocate to the nucleus and regulate gene expression.

Clinical significance

Mutations in the ACVR1 gene are associated with Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition characterized by progressive ossification of soft tissues. In FOP patients, a specific mutation in ACVR1 results in a constitutively active ALK2 protein, leading to inappropriate activation of bone morphogenetic protein (BMP) signaling pathways and abnormal bone formation.

Research

Research into ALK2 has focused on understanding its role in normal cellular processes and disease states, as well as developing therapies for conditions such as FOP. Inhibitors of ALK2, such as LDN-193189 and dorsomorphin, have been developed and are being studied for their potential therapeutic effects.

See also

• Transforming growth factor beta
• Fibrodysplasia ossificans progressiva
• Bone morphogenetic protein