Abstract
MPP7, a previously uncharacterized member of the p55 Stardust family of membrane-associated guanylate kinase (MAGUK) proteins, was found in a tripartite complex with DLG1 and LIN7A or LIN7C. MPP7 dimerizes with all three LIN7 family members (LIN7A, -B, and -C) through interaction of the single L27 domain of LIN7 with the carboxyl-terminal L27 domain of MPP7, thereby stabilizing both proteins. The dimer of MPP7 with LIN7A or LIN7C associates with DLG1 through an interaction requiring the amino-terminal L27 domain of MPP7. The amino-terminal L27 domain of MPP7 is not sufficient for interaction with DLG1 but interacts efficiently only if MPP7 is in a complex with LIN7A or -C. Thus the specificity of interaction of DLG1 with the LIN7-MPP7 complex is determined by L27 interactions with both MPP7 and LIN7. The tripartite complex forms in a ratio of 1:1:1 and localizes to epithelial adherens junctions in a manner dependent upon MPP7. Expression of MPP7 stabilizes DLG1 in an insoluble compartment. Expression of MPP7 deleted of the PDZ or Src homology 3 domain redistributes MPP7, DLG1, and LIN7 out of adherens junctions and into the soluble cytoplasmic fraction without changing the localization of E-cadherin. Thus, the stability and localization of DLG1 to cell-cell junctions are complex functions determined by the expression and association of particular Stardust family members together with particular LIN7 family members.
Highlights
Terminus of interacting proteins), an SH3 domain, and a GUK domain that serve as docking sites for cellular proteins
We have focused this study upon the uncharacterized MPP7 protein and its interaction with DLG1 and LIN7
MPP7 was found in a complex with cellular proteins isolated through affinity for the PDZ ligand of HPV-16 E6
Summary
Terminus of interacting proteins), an SH3 domain, and a GUK domain (catalytically inactive guanylate kinase domain) that serve as docking sites for cellular proteins. The E4orf protein is required to cause rat mammary mesenchymal sarcomas and myoepitheliomas by adenovirus type 9 (16 –18); E4orf contains a PDZ ligand that interacts with a number of cellular PDZ proteins at adherens and tight junctions [19], and this ligand is required for the transformation of rat mammary cells by E4orf1 [20]. Transgenic expression of E6 oncoproteins within the mouse skin is sufficient to induce epithelial hyperplasia and focal squamous cell carcinomas; analysis of E6 mutants established that this phenotype requires the presence of a PDZ ligand at the carboxyl terminus of E6. This implicates cellular PDZ proteins as targets for E6 oncogenicity
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