Negative-feedback regulation of the Wnt pathway by conductin/axin2 involves insensitivity to upstream signalling.
Axin and conductin (also known as axin2) are structurally related inhibitors of Wnt/β-catenin signalling that promote degradation of β-catenin. Whereas axin is constitutively expressed, conductin is a Wnt target gene implicated in Wnt negative-feedback regulation. Here, we show that axin and conductin differ in their functional interaction with the upstream Wnt pathway component Dvl. Conductin shows reduced binding to Dvl2 compared to axin, and degradation of β-catenin by conductin is only poorly blocked by Dvl2. We propose that insensitivity to Dvl is an important feature of the role of conductin as a negative-feedback regulator of Wnt signalling.
Nikolaus-Fiebiger-Center, Chair of Experimental Medicine II, Friedrich-Alexander Universität Erlangen-Nürnberg, Glückstr. 6, D-91054 Erlangen, Germany.
Dominic B
DB
Bernkopf
Nikolaus-Fiebiger-Center, Chair of Experimental Medicine II, Friedrich-Alexander Universität Erlangen-Nürnberg, Glückstr. 6, D-91054 Erlangen, Germany.
Michel V
MV
Hadjihannas
Nikolaus-Fiebiger-Center, Chair of Experimental Medicine II, Friedrich-Alexander Universität Erlangen-Nürnberg, Glückstr. 6, D-91054 Erlangen, Germany jbehrens@molmed.uni-erlangen.de.
Jürgen
J
Behrens
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D000072261:Dishevelled Proteins; D057809:HEK293 Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
C491761:AXIN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins
Axin; Conductin; Dvl; Negative feedback; Wnt