Discoidin domain-containing receptor 2 (DDR2) (DDR2)

Discoidin domain-containing receptor 2 (DDR2) is a unique member of the receptor tyrosine kinase (RTK) family that is activated by fibrillar collagens, particularly Type I collagen, rather than soluble growth factors (UniProt: P36888). In tenocytes, DDR2 serves as a critical sensor of the extracellular matrix (ECM) environment, mediating cellular responses to mechanical stress and injury (PubMed: 21633954). Upon activation, DDR2 triggers signaling cascades that regulate the expression of matrix metalloproteinases (MMPs), which are essential for the remodeling of the collagenous matrix. Dysregulation of the DDR2-collagen axis is a significant factor in the development of tendinopathy and other fibroproliferative diseases, where it contributes to pathological matrix degradation and fibrosis (PubMed: 28938308). Furthermore, DDR2 is implicated in cancer progression, specifically in promoting tumor cell invasion and metastasis through its interaction with the surrounding collagen-rich stroma. Therapeutic strategies targeting DDR2 often utilize small-molecule kinase inhibitors like dasatinib, which compete for the ATP-binding site of the receptor to block its signaling activity (DrugBank: DB01254). Understanding the specific role of DDR2 on tenocytes provides insights into potential treatments for chronic tendon injuries and age-related degenerative conditions.

Other names

CD167 antigen-like family member BTyrosine-protein kinase TKTTyrosine kinase orphan receptor 10Neurotrophic tyrosine kinase receptor-related 3CD167bDiscoidin domain receptor 2

Small molecule inhibition of the intracellular tyrosine kinase domain, which prevents collagen-induced autophosphorylation and subsequent downstream signaling pathways such as Shc and MAPK (DrugBank: DB01254).