The PDZ-binding motif of MCC is phosphorylated at position −1 and controls lamellipodia formation in colon epithelial cells
Copyright policy )The PDZ-binding motif of MCC is phosphorylated at position −1 and controls lamellipodia formation in colon epithelial cells
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.
- UNSW Sydney Australia
- Garvan Institute of Medical Research Australia
- St Vincent's Hospital Sydney Australia
Colon, Amino Acid Motifs, Molecular Sequence Data, PDZ Domains, Phosphoserine, Cell Line, Tumor, Humans, PDZ, Amino Acid Sequence, Pseudopodia, Phosphorylation, Scrib, Molecular Biology, MCC, Nonmuscle Myosin Type IIB, PDZ-binding motif, Cell Membrane, Cell Polarity, Membrane Proteins, Epithelial Cells, Cell Biology, Lamellipodia, Protein Transport, Amino Acid Substitution, Mutation, Myosin-IIB, Mutant Proteins, Protein Binding
Colon, Amino Acid Motifs, Molecular Sequence Data, PDZ Domains, Phosphoserine, Cell Line, Tumor, Humans, PDZ, Amino Acid Sequence, Pseudopodia, Phosphorylation, Scrib, Molecular Biology, MCC, Nonmuscle Myosin Type IIB, PDZ-binding motif, Cell Membrane, Cell Polarity, Membrane Proteins, Epithelial Cells, Cell Biology, Lamellipodia, Protein Transport, Amino Acid Substitution, Mutation, Myosin-IIB, Mutant Proteins, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).27 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!