Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3.
The extracellular signal-regulated kinase (ERK) is a key transducer of the epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) signaling pathways, and its function is required in multiple processes during animal development. The activity of ERK depends on the phosphorylation state of conserved threonine and tyrosine residues, and this state is regulated by different kinases and phosphatases. A family of phosphatases with specificity toward both threonine and tyrosine residues in ERK (dual-specificity phosphatases) play a conserved role in its dephosphorylation and consequent inactivation. Here, we characterize the function of the dual-specificity phosphatase MKP3 in Drosophila EGFR and Xenopus FGFR signaling. The function of MKP3 is required during Drosophila wing vein formation and Xenopus anteroposterior neural patterning. We find that the expression of the MKP3 gene is localized in places of high EGFR and FGFR signaling. Furthermore, this restricted expression depends on ERK function both in Drosophila and Xenopus, suggesting that MKP3 constitutes a conserved negative feedback loop on the activity of the Ras/ERK signaling pathway.
Gómez
Ana Ruiz
AR
Centro de Biologóa Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
López-Varea
Ana
A
Molnar
Cristina
C
de la Calle-Mustienes
Elisa
E
Ruiz-Gómez
Mar
M
Gómez-Skarmeta
José Luis
JL
de Celis
Jose F
JF
D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning; D020134:Catalytic Domain; D002874:Chromosome Mapping; D004330:Drosophila / Q000196:embryology*; D004625:Embryo, Nonmammalian; D066246:ErbB Receptors / Q000378:metabolism; D005091:Exons; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D007438:Introns; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D014680:Veins / Q000254:growth & development; D014921:Wings, Animal / Q000254:growth & development; D014981:Xenopus / Q000196:embryology*; D018631:ras Proteins / Q000378:metabolism*
D015415:Biomarkers; D017468:Receptors, Fibroblast Growth Factor; D013912:Threonine; D014443:Tyrosine; D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins