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PMID:21238927

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Citation

Zand, TP, Reiner, DJ and Der, CJ (2011) Ras effector switching promotes divergent cell fates in C. elegans vulval patterning. Dev. Cell 20:84-96

Abstract

The C. elegans vulva is patterned by epidermal growth factor (EGF) activation of Ras to control 1° fate, and 1° fate induces antagonistic Notch-dependent 2° fate. Furthermore, a spatial EGF gradient, in addition to inducing 1° fate, directly contributes to 2° fate via an unknown pathway. We find that in addition to its canonical effector, Raf, vulval Ras utilizes an exchange factor for the Ral small GTPase (RalGEF), such that Ras-RalGEF-Ral antagonizes Ras-Raf pro-1° fate activity. Consistent with its restricted expression pattern, Ral participates in EGF pro-2° activity. Thus, we have delineated a Ras effector-switching mechanism whereby position within the morphogen gradient dictates that Ras effector usage is switched to RalGEF from Raf to promote 2° instead of 1° fate. Our observations define the utility of Ras effector switching during normal development and may provide a possible mechanistic basis for cell and cancer-type differences in effector dependency and activation.

Links

PubMed PMC3028984 Online version:10.1016/j.devcel.2010.12.004

Keywords

Amino Acid Sequence; Animals; Body Patterning; Caenorhabditis elegans/chemistry; Caenorhabditis elegans/cytology; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/growth & development; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/metabolism; Cell Lineage; Epidermal Growth Factor/metabolism; Female; Models, Biological; Molecular Sequence Data; Receptor, Epidermal Growth Factor/metabolism; Receptors, Notch/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Vulva/cytology; Vulva/growth & development; Vulva/metabolism; raf Kinases/metabolism; ral Guanine Nucleotide Exchange Factor/chemistry; ral Guanine Nucleotide Exchange Factor/metabolism; ras Proteins/metabolism

Significance

Annotations

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

CAEEL:G4SFM6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:G4SFM6

enables

GO:0030695: GTPase regulator activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q12967

F

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:G4SFM6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:G4SFM6

located_in

GO:0016020: membrane

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q12967

C

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:H2L0Q6

located_in

GO:0005886: plasma membrane

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P11234

C

Seeded From UniProt

complete

CAEEL:H2L0Q6

enables

GO:0003924: GTPase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P11234

F

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:Q19852

enables

GO:0030695: GTPase regulator activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q12967

F

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:Q19852

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:Q19852

located_in

GO:0016020: membrane

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q12967

C

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0040026: positive regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003030

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002992

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002335

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002299

P

Seeded From UniProt

complete

CAEEL:Q9N3F8

located_in

GO:0005886: plasma membrane

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P11234

C

Seeded From UniProt

complete

CAEEL:Q9N3F8

enables

GO:0003924: GTPase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P11234

F

Seeded From UniProt

complete


See also

References

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