- Tytuł:
- PDZ domain from Dishevelled - a specificity study
- Autorzy:
-
Śmietana, Katarzyna
Mateja, Agnieszka
Krężel, Artur
Otlewski, Jacek - Powiązania:
- https://bibliotekanauki.pl/articles/1039926.pdf
- Data publikacji:
- 2011
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
Dishevelled
Cl2FlAsH-EDT2
NES
nuclear export signal
PDZ
Wnt - Opis:
- Intracellular signaling cascades induced by Wnt proteins play a key role in developmental processes and are implicated in cancerogenesis. It is still unclear how the cell determines which of the three possible Wnt response mechanisms should be activated, but the decision process is most likely dependent on Dishevelled proteins. Dishevelled family members interact with many diverse targets, however, molecular mechanisms underlying these binding events have not been comprehensively described so far. Here, we investigated the specificity of the PDZ domain from human Dishevelled-2 using C-terminal phage display, which led us to identification of a leucine-rich binding motif strongly resembling the consensus sequence of a nuclear export signal. PDZ interactions with several peptide and protein motifs (including the nuclear export signal sequence from Dishevelled-2 protein) were investigated in detail using fluorescence spectroscopy, mutational analysis and immunoenzymatic assays. The experiments showed that the PDZ domain can bind the nuclear export signal sequence of the Dishevelled-2 protein. Since the intracellular localization of Dishevelled is governed by nuclear localization and nuclear export signal sequences, it is possible that the intramolecular interaction between PDZ domain and the export signal could modulate the balance between nuclear and cytoplasmic pool of the Dishevelled protein. Such a regulatory mechanism would be of utmost importance for the differential activation of Wnt signaling cascades, leading to selective promotion of the nucleus-dependent Wnt β-catenin pathway at the expense of non-canonical Wnt signaling.
- Źródło:
-
Acta Biochimica Polonica; 2011, 58, 2; 243-250
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł