Domains of axin and disheveled required for interaction and function in wnt signaling.
Disheveled blocks the degradation of beta-catenin in response to Wnt signal by interacting with the scaffolding protein, Axin. To define this interaction in detail we undertook a mutational and binding analysis of the murine Axin and Disheveled proteins. The DIX domain of Axin was found to be important for association with Disheveled and two other regions of Axin (between residues 1-168 and 600-810) were identified that can promote the association of Axin and Disheveled. We found that the DIX domain of Disheveled is critical for association with Axin in vivo and for Disheveled activity. The Disheveled DIX domain controlled the ability of Disheveled to induce the accumulation of cytosolic beta-catenin whereas the PDZ domain was not essential to this function.
Julius
M A
MA
Department of Pathology, Department of OB/GYN, Department of Genetics and Development, Columbia University, 630 West 168 Street, New York, New York, 10032, USA.
Schelbert
B
B
Hsu
W
W
Fitzpatrick
E
E
Jho
E
E
Fagotto
F
F
Costantini
F
F
Kitajewski
J
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein; D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction; D013816:Thermodynamics; D015534:Trans-Activators; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin