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PMID:18077345

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Citation

Feng, Y and Irvine, KD (2007) Fat and expanded act in parallel to regulate growth through warts. Proc. Natl. Acad. Sci. U.S.A. 104:20362-7

Abstract

The conserved Drosophila tumor suppressors Fat and Expanded have both recently been implicated in regulating the activity of the Warts tumor suppressor. However, there has been disagreement as to the nature of the links among Fat, Expanded, and Warts and the significance of these links to growth control. We report here that mutations in either expanded or fat can be rescued to viability simply by overexpressing Warts, indicating that their essential function is their influence on Warts rather than reported effects on endocytosis or other pathways. These rescue experiments also separate the transcriptional from the planar cell polarity branches of Fat signaling and reveal that Expanded does not directly affect polarity. We also investigate the relationship between expanded and fat and show, contrary to prior reports, that they have additive effects on imaginal disk growth and development. Although mutation of fat can cause partial loss of Expanded protein from the membrane, mutation of fat promotes growth even when Expanded is overexpressed and accumulates at its normal subapical location. These observations argue against recent proposals that Fat acts simply as a receptor for the Hippo signaling pathway and instead support the proposal that Fat and Expanded can act in parallel to regulate Warts through distinct mechanisms.

Links

PubMed PMC2154436 Online version:10.1073/pnas.0706722105

Keywords

Animals; Cell Adhesion Molecules/analysis; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Drosophila/growth & development; Drosophila/metabolism; Drosophila Proteins/analysis; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Intracellular Signaling Peptides and Proteins; Membrane Proteins/analysis; Membrane Proteins/genetics; Membrane Proteins/metabolism; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/metabolism

Significance

Annotations

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

DROME:FAT

involved_in

GO:0046621: negative regulation of organ growth

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011739

P

Seeded From UniProt

complete

DROME:FAT

involved_in

GO:0035332: positive regulation of hippo signaling

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011739

P

Seeded From UniProt

complete

DROME:FAT

involved_in

GO:0001736: establishment of planar polarity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:EXPA

located_in

GO:0016327: apicolateral plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0046621: negative regulation of organ growth

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011739

P

Seeded From UniProt

complete

DROME:EXPA

involved_in

GO:0035332: positive regulation of hippo signaling

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011739

P

Seeded From UniProt

complete


See also

References

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