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PMID:21238927
| 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 |
| edit table |
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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