ArticleProceedings of the National Academy of Sciences of the United States of America2019
Optimizing photoswitchable MEK.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- A transgenic zebrafish for spatiotemporal optogenetic activation of FGF/ERK signaling.Biology open · 2026Article
- An optogenetic toolkit for robust activation of FGF, BMP, & Nodal signaling in zebrafish.Developmental biology · 2026Article
- A transgenic zebrafish for direct optogenetic activation of FGF/ERK signaling.bioRxiv : the preprint server for biology · 2026Article
- Lights up on the embryonic dance: tools and applications of optogenetics in developmental biology.Genes & development · 2026Review
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Optogenetic control of transition to metamorphosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Disrupted developmental signaling induces novel transcriptional states.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synergistic and independent roles for Nodal and FGF in zebrafish cardiac progenitor cell migration and asymmetric heart morphogenesis.Development (Cambridge, England) · 2025Article
- Phased ERK responsiveness and developmental robustness regulate teleost skin morphogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor.Molecular medicine (Cambridge, Mass.) · 2024Article
- Activating mutations drive human MEK1 kinase using a gear-shifting mechanism.The Biochemical journal · 2023Article
- Optogenetic Signaling Activation in Zebrafish Embryos.Journal of visualized experiments : JoVE · 2023Article
- Light-switchable transcription factors obtained by direct screening in mammalian cells.Nature communications · 2023Article
- Synthetic developmental biology: New tools to deconstruct and rebuild developmental systems.Seminars in cell & developmental biology · 2023Review
- CDK6 activity in a recurring convergent kinase network motif.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Using Optogenetics to Model Cellular Effects of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Development and Application of Opto-Chemical Tools in the Zebrafish.Molecules (Basel, Switzerland) · 2022Review
- A kinase translocation reporter reveals real-time dynamics of ERK activity in Drosophila.Biology open · 2022Article
- Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.Cell reports · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Optogenetic approaches are transforming quantitative studies of cell-signaling systems. A recently developed photoswitchable mitogen-activated protein kinase kinase 1 (MEK1) enzyme (psMEK) short-circuits the highly conserved Extracellular Signal-Regulated Kinase (ERK)-signaling cascade at the most proximal step of effector kinase activation. However, since this optogenetic tool relies on phosphorylation-mimicking substitutions in the activation loop of MEK, its catalytic activity is predicted to be substantially lower than that of wild-type MEK that has been phosphorylated at these residues. Here, we present evidence that psMEK indeed has suboptimal functionality in vivo and propose a strategy to circumvent this limitation by harnessing gain-of-function, destabilizing mutations in MEK. Specifically, we demonstrate that combining phosphomimetic mutations with additional mutations in MEK, chosen for their activating potential, restores maximal kinase activity in vitro. We establish that this modification can be tuned by the choice of the destabilizing mutation and does not interfere with reversible activation of psMEK in vivo in both
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.