title: The PDZ-binding motif of MCC is phosphorylated at position -1 and controls lamellipodia formation in colon epithelial cells.
abstract: In this study, we describe a new post-translational modification at position -1 of the PDZ-binding motif in the mutated in colorectal cancer (MCC) protein and its role in lamellipodia formation. Serine 828 at position -1 of this motif is phosphorylated, which is predicted to increase MCC binding affinity with the polarity protein Scrib. We show that endogenous MCC localizes at the active migratory edge of cells, where it interacts with Scrib and the non-muscle motor protein Myosin-IIB. Expression of MCC harboring a phosphomimetic mutation MCC-S828D strongly impaired lamellipodia formation and resulted in accumulation of Myosin-IIB in the membrane cortex fraction. We propose that MCC regulates lamellipodia formation by binding to Scrib and its downstream partner Myosin-IIB in a multiprotein complex. Importantly, we propose that the function of this complex is under the regulation of a newly described phosphorylation of the PDZ-binding motif at position -1.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia. l.pangon@garvan.org.au
authors.forename: Laurent
authors.initials: L
authors.lastname: Pangon
authors.forename: Christa
authors.initials: C
authors.lastname: Van Kralingen
authors.forename: Melissa
authors.initials: M
authors.lastname: Abas
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Daly
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: Maija R J
authors.initials: MR
authors.lastname: Kohonen-Corish
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003106:Colon / Q000166:cytology*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D054731:PDZ Domains; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D050505:Mutant Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; C067857:MCC protein, human; D010768:Phosphoserine; D024501:Nonmuscle Myosin Type IIB