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Sci. STKE, 11 March 2003
Vol. 2003, Issue 173, p. tw100
[DOI: 10.1126/stke.2003.173.tw100]


Receptors Signaling by Clipped Delta and Jagged Proteins?

When the receptor Notch binds to its ligands, Delta, Serrate, and Jagged, the receptor is clipped first in an extracellular domain and chopped again by the protease presenilin in an intracellular domain. This releases the soluble cytoplamic domain, which moves to the nucleus to activate gene transcription. Ikeuchi and Sisodia now report that similar processing appears to occur on the ligands Delta1 and Jagged2. In a mouse neuroblastoma cell line that stably expressed Myc-tagged Delta1, the authors observed the presence of a proteolytic fragment of Delta1 that was no longer present if cells were treated with a pharmacological inhibitor of the presenilin protease. Similar results were obtained with Jagged2. Furthermore, when human embryonic kidney cells were transfected with a construct in which Delta1 was fused with the Gal4VP16 transcriptional activator, transcription of a reporter plasmid was detected and such transcription was blocked by the protease inhibitor. Although activation of Delta or Jagged processing through interaction with Notch or a physiological effect of such signaling remains to be established, the findings prompt the intriguing speculation that Delta1 and Jagged2 could function as both ligands and receptors that transmit their own signals by a mechanism similar to that implicated in Notch signaling.

T. Ikeuchi, S. S. Sisodia, The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "{gamma}-secretase" cleavage. J. Biol. Chem. 278, 7751-7754 (2003). [Abstract] [Full Text]

Citation: Signaling by Clipped Delta and Jagged Proteins? Sci. STKE 2003, tw100 (2003).

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