title: The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring.
abstract: BACKGROUND
  The human homologue of the Drosophila Discs-large tumor suppressor protein, hDlg, is a multi-domain cytoplasmic protein that localizes to the membrane at intercellular junction sites. At both synaptic junctions and epithelia cell-cell junctions, hDlg is known to recruit several signaling proteins into macromolecular complexes. hDlg is also found at the midbody, a small microtubule-rich structure bridging the two daughter cells during cytokinesis, but its function at this site is not clear.
  
  
  RESULTS
  Here we describe the interaction of hDlg with the activated form of MEK2 of the canonical RAF/MEK/ERK pathway, a protein that is found at the midbody during cytokinesis. We show that both proteins localize to a sub-structure of the midbody, the midbody ring, and that the interaction between the PDZ domains of hDlg and the C-terminal portion of MEK2 is dependent on the phosphorylation of MEK2. Finally, we found that E-cadherin also localizes to the midbody and that its expression is required for the isoform-specific recruitment of hDlg, but not activated MEK2, to that structure.
  
  
  CONCLUSIONS
  Our results suggest that like at other cell-cell junction sites, hDlg is part of a macromolecular complex of structural and signaling proteins at the midbody.
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gaudet
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Langlois
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lue
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rivard
authors.forename: Alain
authors.initials: A
authors.lastname: Viel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis; D000074288:Discs Large Homolog 1 Protein; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D054731:PDZ Domains; D011485:Protein Binding; D016415:Sequence Alignment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; C482128:MAP2K2 protein, human; D048370:MAP Kinase Kinase 2