Characterization of Function of Three Domains in Dishevelled-1: DEP Domain is Responsible for Membrane Translocation of Dishevelled-1  

作　　者：WeiJunPAN ShuZhaoPANG TaoHUANG HuiYunGUO DianqingWU LinLI 

机构地区：[1]LaboratoryofMolecularCellBiology,InstituteofBiochemistryandCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,GraduateSchooloftheChineseAcademyofSciences,320YueyangRd,Shanghai200031 [2]CollegeofLifeScience,JilinUniversity,Changchun130061,China. [3]DepartmentofGeneticsandDevelopmentalBiology,UniversityofConnecticutHealthCenter,Farmington,Connecticut06030,USA.

出　　处：《Cell Research》2004年第4期324-330,共7页细胞研究（英文版）

摘　　要：Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl) protein was considered as the intersection of Wnt signal traffic. In this study, we characterized the function of three domains (DIX,PDZ and DEP) of Dvl-1 in canonical Wnt signal transduction and Dvl-1 membrane translocation. It was found both DIX and DEP domain were sufficient to block Wnt-3a-induced LEF-1 transcriptional activity and free cytosol β-catenin accumulation; whereas PDZ domain and a functional mutant form of DEP domain (DEP-KM) had no effect on canonical Wnt signaling. In addition, when cotransfected with Fz-7, DEP domain, but not DIX, PDZ or DEP-KM, translocated and co-localized with Fz-7 to the plasma membrane, which was similar to Dvl-1. Furthermore, it was DEP domain that could block Fz-7-induced membrane translocation of Dvl- 1 via a possible competitive mechanism. These results strongly suggest that DEP domain is responsible for the membrane translocation of Dvl-1 protein upon Wnt signal stimulation.

关 键 词：Wnt frizzled-7 DISHEVELLED DIX PDZ DEP membrane translocation signal transduction 

分 类 号：Q26[生物学—细胞生物学] Q73