Structural requirements for notch signalling with delta and serrate during the development and patterning of the wing disc of Drosophila.
The delta and Serrate proteins interact with the extracellular domain of the Notch receptor and initiate signalling through the receptor. The two ligands are very similar in structure and have been shown to be interchangeable experimentally; however, loss of function analysis indicates that they have different functions during development and analysis of their signalling during wing development indicates that the Fringe protein can discriminate between the two ligands. This raises the possibility that the signalling of delta and Serrate through Notch requires different domains of the Notch protein. Here we have tested this possibility by examining the ability of delta and Serrate to interact and signal with Notch molecules in which different domains had been deleted. This analysis has shown that EGF-like repeats 11 and 12, the RAM-23 and cdc10/ankyrin repeats and the region C-terminal to the cdc10/ankyrin repeats of Notch are necessary for both delta and Serrate to signal via Notch. They also indicate, however, that delta and Serrate utilise EGF-like repeats 24-26 of Notch for signalling, but there are significant differences in the way they utilise these repeats.
Lawrence
N
N
Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
Klein
T
T
Brennan
K
K
Martinez Arias
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D019521:Body Patterning; D002135:Calcium-Binding Proteins; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins; D004815:Epidermal Growth Factor / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051880:Receptors, Notch; D020449:Repetitive Sequences, Amino Acid; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development* / Q000378:metabolism
D017487:Ankyrins; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; C064045:delta protein; D004815:Epidermal Growth Factor