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A genome-scale approach for determining the function of phosphorylation sites

Combining post-translational modification site-centric base editing with phenotypic screens uncovers the function of phosphorylation sites in high throughput, enabling the study of expansive signaling networks at a speed comparable to that of functional genomics.

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Fig. 1: Identification of kinases that modulate NFAT transcriptional activity during T cell activation.

References

  1. Needham, E. J., Parker, B. L., Burykin, T., James, D. E. & Humphrey, S. J. Illuminating the dark phosphoproteome. Sci. Signal. 12, eaau8645 (2019). Review of how many phosphosites have remained unstudied.

    Article  CAS  PubMed  Google Scholar 

  2. Yeh, W.-H., Chiang, H., Rees, H. A., Edge, A. S. B. & Liu, D. R. In vivo base editing of post-mitotic sensory cells. Nat. Commun. 9, 2184 (2018). Describes how mutation of a single phosphosite alters cell biology in auditory sensory cells.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schmidt, R. et al. Base-editing mutagenesis maps alleles to tune human T cell functions. Nature 625, 805–812 (2024). Large-scale base editing to mutate all of the amino acids in select proteins involved in TCR signaling in primary human T cells.

    Article  CAS  PubMed  Google Scholar 

  4. Johnson, J. L. et al. An atlas of substrate specificities for the human serine/threonine kinome. Nature 613, 759–766 (2023). Repository of in vitro kinase assays coupled to synthetic peptides to determine sequence preferences for serine/threonine kinases.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This is a summary of: Kennedy, P. H. et al. Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput. Nat. Methods https://doi.org/10.1038/s41592-024-02256-z (2024).

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A genome-scale approach for determining the function of phosphorylation sites. Nat Methods (2024). https://doi.org/10.1038/s41592-024-02264-z

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