دورية أكاديمية
An atlas of substrate specificities for the human serine/threonine kinome
| العنوان: | An atlas of substrate specificities for the human serine/threonine kinome |
|---|---|
| المؤلفون: | Johnson, Jared L., Yaron, Tomer M., Huntsman, Emily M., Kerelsky, Alexander, Song, Junho, Regev, Amit, Lin, Ting-Yu, Liberatore, Katarina, Cizin, Daniel M., Cohen, Benjamin M., Vasan, Neil, Ma, Yilun, Krismer, Konstantin, Torres Robles, Jaylissa, van de Kooij, Bert, van Vlimmeren, Anne E., Andrée-Busch, Nicole, Käufer, Norbert F., Dorovkov, Maxim V., Ryazanov, Alexey G., Takagi, Yuichiro, Kastenhuber, Edward R., Goncalves, Marcus D., Hopkins, Benjamin D., Elemento, Olivier, Taatjes, Dylan J., Maucuer, Alexandre, Yamashita, Akio, Degterev, Alexei, Uduman, Mohamed, Lu, Jingyi, Landry, Sean D., Zhang, Bin, Cossentino, Ian, Linding, Rune, Blenis, John, Hornbeck, Peter V., Turk, Benjamin E., Yaffe, Michael B., Cantley, Lewis C. |
| المساهمون: | Biochemistry and Molecular Biology, School of Medicine |
| المصدر: | PMC |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2023 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Kinases, Cellular signalling networks, Bioinformatics, Phosphorylation |
| الوصف: | Protein phosphorylation is one of the most widespread post-translational modifications in biology (1,2). With advances in mass-spectrometry-based phosphoproteomics, 90,000 sites of serine and threonine phosphorylation have so far been identified, and several thousand have been associated with human diseases and biological processes (3,4). For the vast majority of phosphorylation events, it is not yet known which of the more than 300 protein serine/threonine (Ser/Thr) kinases encoded in the human genome are responsible (3). Here we used synthetic peptide libraries to profile the substrate sequence specificity of 303 Ser/Thr kinases, comprising more than 84% of those predicted to be active in humans. Viewed in its entirety, the substrate specificity of the kinome was substantially more diverse than expected and was driven extensively by negative selectivity. We used our kinome-wide dataset to computationally annotate and identify the kinases capable of phosphorylating every reported phosphorylation site in the human Ser/Thr phosphoproteome. For the small minority of phosphosites for which the putative protein kinases involved have been previously reported, our predictions were in excellent agreement. When this approach was applied to examine the signalling 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 intrinsic substrate specificity of the human Ser/Thr kinome, illuminate cellular signalling responses and provide a resource to link phosphorylation events to biological pathways. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Nature; Johnson JL, Yaron TM, Huntsman EM, et al. An atlas of substrate specificities for the human serine/threonine kinome. Nature. 2023;613(7945):759-766. doi:10.1038/s41586-022-05575-3; https://hdl.handle.net/1805/36481Test |
| الإتاحة: | https://doi.org/10.1038/s41586-022-05575-3Test https://hdl.handle.net/1805/36481Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.D00C2144 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |