title: Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src.
abstract: BACKGROUND
  Desmoglein 3 (Dsg3), a desmosomal adhesion protein, is expressed in basal and immediate suprabasal layers of skin and across the entire stratified squamous epithelium of oral mucosa. However, increasing evidence suggests that the role of Dsg3 may involve more than just cell-cell adhesion.
  
  
  RESULTS
  To determine possible additional roles of Dsg3 during epithelial cell adhesion we used overexpression of full-length human Dsg3 cDNA, and RNAi-mediated knockdown of this molecule in various epithelial cell types. Overexpression of Dsg3 resulted in a reduced level of E-cadherin but a colocalisation with the E-cadherin-catenin complex of the adherens junctions. Concomitantly these transfected cells exhibited marked migratory capacity and the formation of filopodial protrusions. These latter events are consistent with Src activation and, indeed, Src-specific inhibition reversed these phenotypes. Moreover Dsg3 knockdown, which also reversed the decreased level of E-cadherin, partially blocked Src phosphorylation.
  
  
  CONCLUSIONS
  Our data are consistent with the possibility that Dsg3, as an up-stream regulator of Src activity, helps regulate adherens junction formation.
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
authors.forename: Siu Man
authors.initials: SM
authors.lastname: Tsang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
authors.forename: Ann
authors.initials: A
authors.lastname: Wheeler
authors.forename: Richard
authors.initials: R
authors.lastname: Grose
authors.forename: Ian R
authors.initials: IR
authors.lastname: Hart
authors.forename: David R
authors.initials: DR
authors.lastname: Garrod
authors.forename: Farida
authors.initials: F
authors.lastname: Fortune
authors.forename: Hong
authors.initials: H
authors.lastname: Wan
mesh_terms: D000818:Animals; D019556:COS Cells; D000081247:CSK Tyrosine-Protein Kinase; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D051184:Desmoglein 3 / Q000378:metabolism*; D004789:Enzyme Activation; D000939:Epitopes / Q000737:chemistry; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D034622:RNA Interference; D019061:src-Family Kinases
chemical_list: D015820:Cadherins; D051184:Desmoglein 3; D000939:Epitopes; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human