Earticle

초록

영어

Signaling from the Notch receptor family is important in development, and its role in disease has assigned the Notch signaling pathway as a therapeutic target (1). Mammalian Notch receptors are single-pass transmembrane glycoproteins containing 29-36 EGF-like repeats. Notch receptors on "receiving" cells signal when they interact with Notch ligands expressed on "sending" cells. Glycosylation of some Notch EGF-like repeats modulates signaling (2). EGF repeat glycosylation includes constitutive fucosylation of some EGF repeat-localized serine/threonine residues, and elongation of fucose-initiated glycans regulated by the Fringe family of glycosyltransferases (3). We sought to determine how O-fucosylated glycans modulate Notch signaling, using cell-based Notch signaling assay by co-culturing with Notch ligand bearing cells and beads and protein-protein binding assay with surface plasmon resonance (SPR). We find that lunatic Fringe modification of Notch1 receptors enhances Dll1, Dll4, and Jag2 binding affinities and signaling, while it reduces Jag1-mediated binding affinity and signaling. SPR study indicates that Notch signaling is correlated with association constant (KA) and maximum binding capacity (Rmax) may be critical in Notch signaling from Jag2 in solid-phase Notch signaling assay.

저자

• Jeongsup Shim [ Department of Pathology, Genentech, Inc., South San Francisco, 94080, USA ]
• Bronislawa Petryniak [ Department of Pathology, Genentech, Inc., South San Francisco, 94080, USA ]
• John B. Lowe [ Department of Pathology, Genentech, Inc., South San Francisco, 94080, USA ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614