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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-2-17
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pubmed:abstractText |
Zonula occludens (ZO)-1 is a multi-domain scaffold protein known to have critical roles in the establishment of cell-cell adhesions and the maintenance of stable tissue structures through the targeting, anchoring, and clustering of transmembrane adhesion molecules and cytoskeletal proteins. Here, we report that ZO-1 directly binds to MRCK?, a Cdc42 effector kinase that modulates cell protrusion and migration, at the leading edge of migrating cells. Structural studies reveal that the binding of a ? hairpin from GRINL1A converts ZO-1 ZU5 into a complete ZU5-fold. A similar interaction mode is likely to occur between ZO-1 ZU5 and MRCK?. The interaction between ZO-1 and MRCK? requires the kinase to be primed by Cdc42 due to the closed conformation of the kinase. Formation of the ZO-1/MRCK? complex enriches the kinase at the lamellae of migrating cells. Disruption of the ZO-1/MRCK? complex inhibits MRCK?-mediated cell migration. These results demonstrate that ZO-1, a classical scaffold protein with accepted roles in maintaining cell-cell adhesions in stable tissues, also has an active role in cell migration during processes such as tissue development and remodelling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1460-2075
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
665-78
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pubmed:meshHeading |
pubmed-meshheading:21240187-Amino Acid Sequence,
pubmed-meshheading:21240187-Animals,
pubmed-meshheading:21240187-COS Cells,
pubmed-meshheading:21240187-Cell Adhesion,
pubmed-meshheading:21240187-Cell Compartmentation,
pubmed-meshheading:21240187-Cell Movement,
pubmed-meshheading:21240187-Cells, Cultured,
pubmed-meshheading:21240187-Cercopithecus aethiops,
pubmed-meshheading:21240187-Humans,
pubmed-meshheading:21240187-Membrane Proteins,
pubmed-meshheading:21240187-Models, Biological,
pubmed-meshheading:21240187-Models, Molecular,
pubmed-meshheading:21240187-Molecular Sequence Data,
pubmed-meshheading:21240187-Multiprotein Complexes,
pubmed-meshheading:21240187-Phosphoproteins,
pubmed-meshheading:21240187-Protein Binding,
pubmed-meshheading:21240187-Protein Structure, Secondary,
pubmed-meshheading:21240187-Protein Transport,
pubmed-meshheading:21240187-Protein-Tyrosine Kinases,
pubmed-meshheading:21240187-Sequence Homology, Amino Acid,
pubmed-meshheading:21240187-Transfection,
pubmed-meshheading:21240187-cdc42 GTP-Binding Protein
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pubmed:year |
2011
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pubmed:articleTitle |
Cdc42-dependent formation of the ZO-1/MRCK? complex at the leading edge controls cell migration.
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pubmed:affiliation |
Division of Life Science, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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