Jagged2

Jagged2, also known as JAG2, is a protein encoded by the JAG2 gene in humans. It is a member of the Jagged family of ligands in the Notch signaling pathway, functioning as a transmembrane ligand that activates Notch receptors on adjacent cells to influence cell fate decisions.

Structurally, Jagged-2 is a type I transmembrane glycoprotein with an extracellular region containing a Delta/Serrate/Lag-2 (DSL) domain and multiple epidermal growth factor (EGF)-like repeats. It has a single transmembrane segment and a cytoplasmic tail. The protein is expressed on the surface of select cell types and interacts primarily with Notch receptors (Notch1–4) to initiate signaling that regulates gene expression.

In development and tissue maintenance, Jagged-2 participates in the regulation of differentiation, morphogenesis, and organ formation. It contributes to the orchestration of Notch signaling in various tissues, including epithelia and neural crest derivatives, and plays a role in processes such as hematopoiesis, thymic development, and tissue homeostasis. The exact effects of Jagged-2 signaling can be context-dependent, varying with cell type, developmental stage, and the complement of Notch receptors present.

Clinical significance of JAG2 perturbations is an area of active research. Altered Jagged-Notch signaling has been associated with developmental abnormalities and with cancer in a tissue-specific manner. In cancer, changes in JAG2 expression have been observed in several tumor types and are being explored for their potential as biomarkers or therapeutic targets, reflecting the broader interest in Notch pathway modulation in oncology.

Further research continues to clarify Jagged-2’s precise roles in development, stem cell regulation, and disease.