Protein Jagged-2 (JAG2)

Protein Jagged-2 (JAG2) is a single-pass type I transmembrane protein that serves as a canonical ligand for the Notch signaling pathway. It is characterized by an extracellular domain containing multiple epidermal growth factor (EGF)-like repeats and a DSL (Delta/Serrate/LAG-2) domain, which is critical for binding to Notch receptors (Notch 1-4). JAG2 is essential for various developmental processes, including limb morphogenesis, inner ear hair cell patterning, and T-cell maturation in the thymus, where it mediates lateral inhibition to specify cell fates. In pathological contexts, JAG2 is frequently upregulated in several cancers, such as multiple myeloma and colorectal cancer, contributing to tumor progression, angiogenesis, and resistance to chemotherapy. Additionally, loss-of-function mutations in the JAG2 gene are associated with limb-girdle muscular dystrophy R27 (LGMDR27), underscoring its role in maintaining the muscle stem cell niche. Therapeutic efforts to modulate JAG2 involve the use of gamma-secretase inhibitors and the development of specific neutralizing antibodies to disrupt the Notch signaling axis, although these approaches must navigate significant safety concerns related to the systemic inhibition of Notch signaling in healthy tissues.

Other names

Jagged2hJ2SER2Jagged canonical Notch ligand 2LGMDR27

Inhibition of Notch signaling by blocking ligand-receptor interaction or preventing proteolytic cleavage of Notch receptors.