Notch2 receptor and Notch3 receptor (NOTCH2, NOTCH3)

The Notch2 receptor and Notch3 receptor are single-pass transmembrane proteins and core components of the Notch signaling pathway, a highly conserved cell-cell communication mechanism essential in regulating cell fate, proliferation, and differentiation during development and tissue homeostasis[5][3][6]. Both receptors undergo a series of proteolytic cleavages (S1 in the Golgi, S2 by ADAM10/17 family proteases, S3 by γ-secretase in the membrane), ultimately releasing the Notch intracellular domain (NICD), which translocates to the nucleus to regulate gene transcription[3][4][5][6]. Notch2 is particularly important for cardiovascular and smooth muscle development, acting as an anti-proliferative signal in vascular smooth muscle and contributing to vascular morphogenesis and maintenance[1][7]. Notch3 is crucial for vascular smooth muscle cell differentiation, survival, and proliferation, with a key role in maintaining arterial integrity and function[7][1]. Dysregulation of Notch2 or Notch3 signaling can contribute to various cancers (e.g., T-ALL, ovarian cancer, glioblastoma), vascular diseases, and developmental disorders[2][5]. Therapeutically, they are targeted by small molecules and antibodies that inhibit Notch processing or ligand interactions, but on-target toxicities remain a challenge due to the receptors' crucial roles in normal tissue function[8][5].

Other names

Neurogenic locus notch homolog protein 2Neurogenic locus notch homolog protein 3

Inhibition of S2 or S3 cleavage to prevent NICD release and downstream gene transcription Blocking ligand-receptor interaction on cell surface to inhibit pathway activation