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PMID:17255944

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Citation

Astigarraga, S, Grossman, R, Díaz-Delfín, J, Caelles, C, Paroush, Z and Jiménez, G (2007) A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling. EMBO J. 26:668-77

Abstract

Early Drosophila development requires two receptor tyrosine kinase (RTK) pathways: the Torso and the Epidermal growth factor receptor (EGFR) pathways, which regulate terminal and dorsal-ventral patterning, respectively. Previous studies have shown that these pathways, either directly or indirectly, lead to post-transcriptional downregulation of the Capicua repressor in the early embryo and in the ovary. Here, we show that both regulatory effects are direct and depend on a MAPK docking site in Capicua that physically interacts with the MAPK Rolled. Capicua derivatives lacking this docking site cause dominant phenotypes similar to those resulting from loss of Torso and EGFR activities. Such phenotypes arise from inappropriate repression of genes normally expressed in response to Torso and EGFR signaling. Our results are consistent with a model whereby Capicua is the main nuclear effector of the Torso pathway, but only one of different effectors responding to EGFR signaling. Finally, we describe differences in the modes of Capicua downregulation by Torso and EGFR signaling, raising the possibility that such differences contribute to the tissue specificity of both signals.

Links

PubMed PMC1794389 Online version:10.1038/sj.emboj.7601532

Keywords

Amino Acid Sequence; Animals; Base Sequence; Binding Sites/genetics; Body Patterning/genetics; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Drosophila/embryology; Drosophila/genetics; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Extracellular Signal-Regulated MAP Kinases/metabolism; Female; Gene Expression Regulation, Developmental; HMGB Proteins; Molecular Sequence Data; Ovary/metabolism; Phosphorylation; Protein Kinases/metabolism; Receptor Protein-Tyrosine Kinases/metabolism; Receptor, Epidermal Growth Factor/metabolism; Receptors, Invertebrate Peptide/metabolism; Repressor Proteins/genetics; Repressor Proteins/metabolism; Sequence Analysis, DNA; Signal Transduction/genetics; Signal Transduction/physiology; Two-Hybrid System Techniques

Significance

Annotations

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

MOUSE:JUN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91Y86

F

Seeded From UniProt

complete

HUMAN:MK01

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9U1H0

F

Seeded From UniProt

complete

DROME:ERKA

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0262582

F

Seeded From UniProt

complete

DROME:ERKA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9U1H0

F

Seeded From UniProt

complete

MOUSE:MK08

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05627

F

Seeded From UniProt

complete

DROME:CIC

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:CIC

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CIC

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:CIC

involved_in

GO:0008293: torso signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CIC

involved_in

GO:0009953: dorsal/ventral pattern formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CIC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P28482

F

Seeded From UniProt

complete

DROME:CIC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P40417

F

Seeded From UniProt

complete


See also

References

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