| RRC ID |
89264
|
| 著者 |
Matsuno K, Ito M, Hori K, Miyashita F, Suzuki S, Kishi N, Artavanis-Tsakonas S, Okano H.
|
| タイトル |
Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling.
|
| ジャーナル |
Development
|
| Abstract |
The Notch pathway is an evolutionarily conserved signaling mechanism that is essential for cell-cell interactions. The Drosophila deltex gene regulates Notch signaling in a positive manner, and its gene product physically interacts with the intracellular domain of Notch through its N-terminal domain. Deltex has two other domains that are presumably involved in protein-protein interactions: a proline-rich motif that binds to SH3-domains, and a RING-H2 finger motif. Using an overexpression assay, we have analyzed the functional involvement of these Deltex domains in Notch signaling. The N-terminal domain of Deltex that binds to the CDC10/Ankyrin repeats of the Notch intracellular domain was indispensable for the function of Deltex. A mutant form of Deltex that lacked the proline-rich motif behaved as a dominant-negative form. This dominant-negative Deltex inhibited Notch signaling upstream of an activated, nuclear form of Notch and downstream of full-length Notch, suggesting the dominant-negative Deltex might prevent the activation of the Notch receptor. We found that Deltex formed a homo-multimer, and mutations in the RING-H2 finger domain abolished this oligomerization. The same mutations in the RING-H2 finger motif of Deltex disrupted the function of Deltex in vivo. However, when the same mutant was fused to a heterologous dimerization domain (Glutathione-S-Transferase), the chimeric protein had normal Deltex activity. Therefore, oligomerization mediated by the RING-H2 finger motif is an integral step in the signaling function of Deltex.
|
| 巻・号 |
129(4)
|
| ページ |
1049-59
|
| 公開日 |
2002-2-1
|
| DOI |
10.1242/dev.129.4.1049
|
| PMID |
11861487
|
| MeSH |
Amino Acid Motifs
Animals
Animals, Genetically Modified
Drosophila / genetics
Drosophila / growth & development
Drosophila Proteins*
Insect Proteins / genetics
Insect Proteins / metabolism
Insect Proteins / physiology*
Membrane Proteins / metabolism*
Mutagenesis
Proline
Receptors, Notch
Signal Transduction*
|
| リソース情報 |
| ショウジョウバエ |
DGRC#119831 |
