A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling.

Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0261-4189 (Print) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE

Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-

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

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.

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GENBANK AAH58665; AAK73515; CAD44099; CAF90910
RefSeq XP_395209

0 (Drosophila Proteins)
0 (HMGB Proteins)
0 (Receptors, Invertebrate Peptide)
0 (Repressor Proteins)
0 (cic protein, Drosophila)
EC 2.7.- (Protein Kinases)
EC 2.7.10.1 (Egfr protein, Drosophila)
EC 2.7.10.1 (ErbB Receptors)
EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
EC 2.7.10.1 (tor protein, Drosophila)
EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
EC 2.7.11.24 (rl protein, Drosophila)

Date Created: 20070127 Date Completed: 20070322 Latest Revision: 20190524

20240829

PMC1794389

10.1038/sj.emboj.7601532

17255944