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Jared Lee Johnson, Tomer M. Yaron, Emily M. Huntsman, Alexander Kerelsky, Junho Song, Amit Regev, Ting-Yu Lin, Katarina M. Liberatore, Daniel M. Cizin, Benjamin M. Cohen and 30 more
Protein phosphorylation is one of the most widespread post-translational modifications in biology. With the advent of mass spectrometry-based phosphoproteomics, more than 200,000 sites of serine and threonine phosphorylation have been reported, of which several thousand have been associated with human diseases and biological processes. For the vast majority of phosphorylation events, it is not yet known which of the more than 300 protein Ser/Thr kinases encoded in the human genome is responsible. Here, we utilize synthetic peptide libraries to profile the substrate sequence specificity of nearly every functional human Ser/Thr kinase. Viewed in its entirety, the substrate specificity of the kinome was substantially more diverse than expected and was driven extensively by negative selectivity. Our kinome-wide dataset was used to computationally annotate and identify the most likely protein kinases for every reported phosphorylation site in the human Ser/Thr phosphoproteome. For the small minority of phosphosites where the protein kinases involved have been previously identified, our predictions were in excellent agreement. When this approach was applied to examine the signaling response of tissues and cell lines to hormones, growth factors, targeted inhibitors, and environmental or genetic perturbations, it revealed unexpected insights into pathway complexity and compensation. Overall, these studies reveal the full extent of substrate specificity of the human Ser/Thr kinome, illuminate cellular signaling responses, and provide a rich resource to link unannotated phosphorylation events to biological pathways.
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Johnson, J. L., Yaron, T. M., Huntsman, E. M., Kerelsky, A., Song, J., Regev, A., Lin, T.-Y., Liberatore, K. M., Cizin, D. M., Cohen, B. M., Vasan, N., Ma, Y., Krismer, K., Robles, J. T., Kooij, B. V. D., Vlimmeren, A. E. V., Andrée-Busch, N., Käufer, N. F., Dorovkov, M. V., … Cantley, L. C. (2023). An atlas of substrate specificities for the human serine/threonine kinome. Nature, 613(7945), 759–766. https://doi.org/10.1038/s41586-022-05575-3
Johnson, Jared Lee, et al. "An atlas of substrate specificities for the human serine/threonine kinome." Nature, vol. 613, no. 7945, 2023, pp. 759–766, https://doi.org/10.1038/s41586-022-05575-3.
Johnson, Jared Lee, Tomer M. Yaron, Emily M. Huntsman, Alexander Kerelsky, Junho Song, Amit Regev, Ting-Yu Lin, et al. "An atlas of substrate specificities for the human serine/threonine kinome." Nature 613, no. 7945 (2023): 759–766. https://doi.org/10.1038/s41586-022-05575-3.
Johnson J. L., Yaron T. M., Huntsman E. M. [и др.] An atlas of substrate specificities for the human serine/threonine kinome // Nature. — 2023. — Vol. 613, № 7945. — P. 759–766. — URL: https://doi.org/10.1038/s41586-022-05575-3
@article{johnson2023atlas,
title = {{An atlas of substrate specificities for the human serine/threonine kinome}},
author = {Jared Lee Johnson and Tomer M. Yaron and Emily M. Huntsman and Alexander Kerelsky and Junho Song and Amit Regev and Ting-Yu Lin and Katarina M. Liberatore and Daniel M. Cizin and Benjamin M. Cohen and Neil Vasan and Yilun Ma and Konstantin Krismer and Jaylissa Torres Robles and Bert van de Kooij and Anne E. van Vlimmeren and Nicole Andrée-Busch and Norbert F. Käufer and Maxim V. Dorovkov and Alexey G. Ryazanov and Yuichiro Takagi and Edward R. Kastenhuber and Marcus DaSilva Goncalves and Benjamin David Hopkins and Olivier Elemento and Dylan J. Taatjes and Alexandre Maucuer and Akio Yamashita and Alexei Degterev and Mohamed Uduman and Jingyi Lu and Sean D. Landry and Bin Zhang and Ian Cossentino and Rune Linding and John Blenis and Peter V. Hornbeck and Benjamin E. Turk and Michael B. Yaffe and Lewis C. Cantley},
journal = {Nature},
year = {2023},
volume = {613},
number = {7945},
pages = {759--766},
doi = {10.1038/s41586-022-05575-3},
url = {https://doi.org/10.1038/s41586-022-05575-3}
}TY - JOUR AU - Johnson, Jared Lee AU - Yaron, Tomer M. AU - Huntsman, Emily M. AU - Kerelsky, Alexander AU - Song, Junho AU - Regev, Amit AU - Lin, Ting-Yu AU - Liberatore, Katarina M. AU - Cizin, Daniel M. AU - Cohen, Benjamin M. AU - Vasan, Neil AU - Ma, Yilun AU - Krismer, Konstantin AU - Robles, Jaylissa Torres AU - Kooij, Bert van de AU - Vlimmeren, Anne E. van AU - Andrée-Busch, Nicole AU - Käufer, Norbert F. AU - Dorovkov, Maxim V. AU - Ryazanov, Alexey G. AU - Takagi, Yuichiro AU - Kastenhuber, Edward R. AU - Goncalves, Marcus DaSilva AU - Hopkins, Benjamin David AU - Elemento, Olivier AU - Taatjes, Dylan J. AU - Maucuer, Alexandre AU - Yamashita, Akio AU - Degterev, Alexei AU - Uduman, Mohamed AU - Lu, Jingyi AU - Landry, Sean D. AU - Zhang, Bin AU - Cossentino, Ian AU - Linding, Rune AU - Blenis, John AU - Hornbeck, Peter V. AU - Turk, Benjamin E. AU - Yaffe, Michael B. AU - Cantley, Lewis C. TI - An atlas of substrate specificities for the human serine/threonine kinome JO - Nature VL - 613 IS - 7945 SP - 759 EP - 766 PY - 2023 DA - 2023/01/11 DO - 10.1038/s41586-022-05575-3 UR - https://doi.org/10.1038/s41586-022-05575-3 ER -
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