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PMID:15195140

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Citation

Yao, R, Natsume, Y and Noda, T (2004) MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap. Oncogene 23:6023-30

Abstract

A seven-transmembrane protein, frizzled, has been implicated in a planar cell polarity (PCP) pathway as well as the canonical Wnt signaling pathway. Although both pathways require a cytoplasmic protein, dishevelled, the molecular mechanism by which frizzled regulates intracellular signaling remains to be elucidated. In the mouse, nine frizzled family members have been identified and six of them contain a PDZ-binding motif at their carboxyl-termini. In this study, we show that a multi-PDZ containing protein, MAGI-3, specifically binds to frizzled-4 and -7. Furthermore, we also demonstrate that MAGI-3 interacts with Ltap, a mouse homolog of the Drosophila PCP protein, stbm, and that these three molecules can form a ternary complex. In epithelial cells, MAGI-3, frizzled-4, and Ltap colocalized at cell contact sites, indicating that these molecules form a physiologically significant complex. Finally, we found that MAGI-3 strongly activated JNK in conjunction with frizzled-4 and Ltap, and that this activation required the small GTPase, Rac. These results indicate that MAGI-3 functions as a scaffold protein for frizzled-4 and Ltap and regulates the JNK signaling cascade.

Links

PubMed Online version:10.1038/sj.onc.1207817

Keywords

Animals; Cell Line; Frizzled Receptors; Guanylate Kinase; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; MAP Kinase Signaling System; Mice; Multiprotein Complexes; Nerve Tissue Proteins/analysis; Nerve Tissue Proteins/metabolism; Nucleoside-Phosphate Kinase/chemistry; Nucleoside-Phosphate Kinase/physiology; Protein Structure, Tertiary; Proteins/analysis; Proteins/metabolism; Receptors, Cell Surface; Receptors, G-Protein-Coupled/metabolism; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CADH1

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FZD4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQJ9

F

Seeded From UniProt

complete

MOUSE:FZD4

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FZD4

acts_upstream_of_or_within

GO:0043507: positive regulation of JUN kinase activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1923484
MGI:MGI:2135272

P

Seeded From UniProt

complete

MOUSE:FZD7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQJ9

F

Seeded From UniProt

complete

MOUSE:VANG2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EQJ9

F

Seeded From UniProt

complete

MOUSE:VANG2

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:VANG2

acts_upstream_of_or_within

GO:0043507: positive regulation of JUN kinase activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:108520
MGI:MGI:1923484

P

Seeded From UniProt

complete

MOUSE:MAGI3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91ZD4

F

Seeded From UniProt

complete

MOUSE:MAGI3

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

MGI:MGI:108570
PR:Q61088

F

Seeded From UniProt

complete

MOUSE:MAGI3

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:MAGI3

acts_upstream_of_or_within

GO:0043507: positive regulation of JUN kinase activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:108520
MGI:MGI:2135272

P

Seeded From UniProt

complete

MOUSE:CADH1

part_of

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FZD5

acts_upstream_of_or_within

GO:0043507: positive regulation of JUN kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FZD8

acts_upstream_of_or_within

GO:0043507: positive regulation of JUN kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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