hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells.
In Drosophila, the tumor suppressor Scribble is localized at the septate junctions of epithelial cells. Its mammalian homologue, hScrib, is a basolateral protein likely associated to proteins of the cell-cell junctions. We report the direct interaction between hScrib and ZO-2, a junction-associated protein. This interaction relies on two PDZ domains of hScrib and on the C-terminal motif of ZO-2. Both proteins localise at cell-cell junctions of epithelial cells. A point mutation in the LRR of hScrib delocalises the protein from the plasma membrane and abrogates the interaction with ZO-2 but not with betaPIX. Tyrosine phosphorylation of hScrib does not impair the interaction with ZO-2. We show a direct link between two junctional proteins that are down-regulated during cancer progression.
Molecular Pharmacology, UMR 599 Inserm-Institut Paoli-Calmettes, 27 boulevard Leï Roure, 13009 Marseille, France.
Jean-Yves
JY
Métais
Christel
C
Navarro
Marie-Josée
MJ
Santoni
Stéphane
S
Audebert
Jean-Paul
JP
Borg
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism; D062827:Zonula Occludens-2 Protein
D008565:Membrane Proteins; C480591:SCRIB protein, human; C569046:TJP2 protein, human; D025521:Tumor Suppressor Proteins; D062827:Zonula Occludens-2 Protein; D014443:Tyrosine