β-arrestin Kurtz inhibits MAPK and Toll signalling in Drosophila development.
β-Arrestins have been implicated in the regulation of multiple signalling pathways. However, their role in organism development is not well understood. In this study, we report a new in vivo function of the Drosophila β-arrestin Kurtz (Krz) in the regulation of two distinct developmental signalling modules: MAPK ERK and NF-κB, which transmit signals from the activated receptor tyrosine kinases (RTKs) and the Toll receptor, respectively. Analysis of the expression of effectors and target genes of Toll and the RTK Torso in krz maternal mutants reveals that Krz limits the activity of both pathways in the early embryo. Protein interaction studies suggest a previously uncharacterized mechanism for ERK inhibition: Krz can directly bind and sequester an inactive form of ERK, thus preventing its activation by the upstream kinase, MEK. A simultaneous dysregulation of different signalling systems in krz mutants results in an abnormal patterning of the embryo and severe developmental defects. Our findings uncover a new in vivo function of β-arrestins and present a new mechanism of ERK inhibition by the Drosophila β-arrestin Krz.
Tipping
Marla
M
Department of Biology, University of Massachusetts Boston, Boston, MA, USA.
Kim
Yoosik
Y
Kyriakakis
Phillip
P
Tong
Mei
M
Shvartsman
Stanislav Y
SY
Veraksa
Alexey
A
D000818:Animals; D019390:Arrestins / Q000378:metabolism* / Q000494:pharmacology; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055786:Gene Knockout Techniques; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D019390:Arrestins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C412169:krz protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C086795:rl protein, Drosophila
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