Protein jagged-2 (JAG2) (JAG2)

Protein jagged-2 (JAG2) is a single-pass type I transmembrane protein that serves as a canonical ligand for Notch receptors, primarily Notch1, Notch2, and Notch3 [3, 8, 11]. It is a vital component of the Notch signaling pathway, which facilitates cell-to-cell communication to regulate cell fate decisions, embryonic development, and tissue homeostasis [1, 10]. JAG2 is particularly essential for the development of the skeletal system, limbs, teeth, and the immune system, where it influences T-cell differentiation and hematopoiesis [3, 11]. In clinical oncology, JAG2 is frequently overexpressed and acts as a driver of tumor progression, metastasis, and chemoresistance in various cancers, including multiple myeloma and colorectal cancer [1, 5, 6]. It also plays a significant role in the tumor microenvironment by promoting immunosuppression through the reprogramming of tumor-associated macrophages [17]. Therapeutic strategies target JAG2 to disrupt its interaction with Notch receptors, utilizing neutralizing monoclonal antibodies or inhibitors of the Notch pathway like gamma-secretase inhibitors [4, 7, 15]. Targeting JAG2 specifically is being investigated as a potentially safer alternative to pan-Notch inhibitors, which are often limited by severe gastrointestinal side effects [5, 6, 16].

Other names

HJ2SER2JAGL2Jagged2Jagged canonical Notch ligand 2LGMDR27

Neutralization of ligand-receptor interaction; inhibition of JAG2-mediated Notch receptor cleavage and downstream signaling activation