ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engineered kinase activation reveals unique morphodynamic phenotypes and associated trafficking for Src family isoforms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Reciprocal regulation of Solo and Src orchestrates Src trafficking to promote mesenchymal cell migration.iScience · 2025Article
- Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation.Journal of visualized experiments : JoVE · 2024Article
- Phase separation of YAP-MAML2 differentially regulates the transcriptome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Engineering memory with an extrinsically disordered kinase.Science advances · 2023Article
- Dissecting protein tyrosine phosphatase signaling by engineered chemogenetic control of its activity.The Journal of cell biology · 2022Article
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- Optogenetic control of Neisseria meningitidis Cas9 genome editing using an engineered, light-switchable anti-CRISPR protein.Nucleic acids research · 2021Article
- Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity.eLife · 2020Article
- Phosphoregulated orthogonal signal transduction in mammalian cells.Nature communications · 2020Article
- Membrane Anchoring of Hck Kinase via the Intrinsically Disordered SH4-U and Length Scale Associated with Subcellular Localization.Journal of molecular biology · 2020Article
- Septin2 mediates podosome maturation and endothelial cell invasion associated with angiogenesis.The Journal of cell biology · 2020Article
- Engineering Optogenetic Protein Analogs.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Spatiotemporal dynamics of GEF-H1 activation controlled by microtubule- and Src-mediated pathways.The Journal of cell biology · 2019Article
- Time-Variant SRC Kinase Activation Determines Endothelial Permeability Response.Cell chemical biology · 2019Article
- Controlling protein conformation with light.Current opinion in structural biology · 2019Review
- Engineering proteins for allosteric control by light or ligands.Nature protocols · 2019Article
- Emerging role for SRC family kinases in junction dynamics during spermatogenesis.Reproduction (Cambridge, England) · 2019Review
- Piezo1 mediates angiogenesis through activation of MT1-MMP signaling.American journal of physiology. Cell physiology · 2019Article
- Intrinsic properties and plasma membrane trafficking route of Src family kinase SH4 domains sensitive to retargeting by HIV-1 Nef.The Journal of biological chemistry · 2018Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The Src kinase family comprises nine homologous members whose distinct expression patterns and cellular distributions indicate that they have unique roles. These roles have not been determined because genetic manipulation has not produced clearly distinct phenotypes, and the kinases' homology complicates generation of specific inhibitors. Through insertion of a modified FK506 binding protein (insertable FKBP12, iFKBP) into the protein kinase isoforms Fyn, Src, Lyn, and Yes, we engineered kinase analogs that can be activated within minutes in living cells (RapR analogs). Combining our RapR analogs with computational tools for quantifying and characterizing cellular dynamics, we demonstrate that Src family isoforms produce very different phenotypes, encompassing cell spreading, polarized motility, and production of long, thin cell extensions. Activation of Src and Fyn led to patterns of kinase translocation that correlated with morphological changes in temporally distinct stages. Phenotypes were dependent on N-terminal acylation, not on Src homology 3 (SH3) and Src homology 2 (SH2) domains, and correlated with movement between a perinuclear compartment, adhesions, and the plasma membrane.
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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.