Processing of the notch ligand delta by the metalloprotease Kuzbanian.
Signaling by the Notch surface receptor controls cell fate determination in a broad spectrum of tissues. This signaling is triggered by the interaction of the Notch protein with what, so far, have been thought to be transmembrane ligands expressed on adjacent cells. Here biochemical and genetic analyses show that the ligand Delta is cleaved on the surface, releasing an extracellular fragment capable of binding to Notch and acting as an agonist of Notch activity. The ADAM disintegrin metalloprotease Kuzbanian is required for this processing event. These observations raise the possibility that Notch signaling in vivo is modulated by soluble forms of the Notch ligands.
Qi
H
H
Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.
Rand
M D
MD
Wu
X
X
Sestan
N
N
Wang
W
W
Rakic
P
P
Xu
T
T
Artavanis-Tsakonas
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology; D011499:Protein Processing, Post-Translational; D051880:Receptors, Notch; D015398:Signal Transduction; D014162:Transfection
D019483:Disintegrins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C064045:delta protein; C100953:KUZ protein, Drosophila; D008666:Metalloendopeptidases