Kinome-wide identification of phosphorylation networks in eukaryotic proteomes

Parca, Luca; Ariano, Bruno; Cabibbo, Andrea; Paoletti, Martina; Tamburrini, Annalaura; Palmeri, Antonio; Ausiello, Gabriele; Helmer-Citterich, Manuela

doi:10.1093/bioinformatics/bty545

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…PhoScan [ 60 ] and phos_pred [ 49 ] were run locally on a Windows laptop, while NetPhorest [ 65 ], NetworKIN [ 66 ], iGPS [ 57 ], GPS [ 61 ], DeepPhos [ 67 ], jEcho [ 68 ], and MusiteDeep [ 50 ] were run locally on a Mac laptop. AKID [ 69 ], PhosphoPICK [ 70 ], NetPhos [ 71 ], Musite [ 62 ], and pkaPS [ 72 ] were accessed via their websites. Tools were set with the lowest threshold if they did not have an option to return scores for all sites.…”

Section: Main Textmentioning

confidence: 99%

Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources

Savage

Zhang

2020

Clin Proteom

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Mass spectrometry-based phosphoproteomics is becoming an essential methodology for the study of global cellular signaling. Numerous bioinformatics resources are available to facilitate the translation of phosphopeptide identification and quantification results into novel biological and clinical insights, a critical step in phosphoproteomics data analysis. These resources include knowledge bases of kinases and phosphatases, phosphorylation sites, kinase inhibitors, and sequence variants affecting kinase function, and bioinformatics tools that can predict phosphorylation sites in addition to the kinase that phosphorylates them, infer kinase activity, and predict the effect of mutations on kinase signaling. However, these resources exist in silos and it is challenging to select among multiple resources with similar functions. Therefore, we put together a comprehensive collection of resources related to phosphoproteomics data interpretation, compared the use of tools with similar functions, and assessed the usability from the standpoint of typical biologists or clinicians. Overall, tools could be improved by standardization of enzyme names, flexibility of data input and output format, consistent maintenance, and detailed manuals.

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Section: Main Textmentioning

confidence: 99%

Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources

Savage

Zhang

2020

Clin Proteom

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“…All our data on the autophosphorylation activity point towards a phosphorylation of RdmS at a tyrosine residue(s), which form acid‐stable phosphomonoesters. Ser/Thr/Tyr kinases play an important role in eukaryotes (Manning et al ., ; Parca et al ., ) but can also be found in Archaea (Aivaliotis et al ., ; Kennelly, ). Thus far, it is not known whether the phosphoryl group is transferred to the regulator protein(s) or whether phosphorylation is just inducing the protein–protein interaction ultimately leading to changes in mts genes expression.…”

Section: Discussionmentioning

confidence: 99%

Thiol‐based redox sensing in the methyltransferase associated sensor kinase RdmS in Methanosarcina acetivorans

Fiege

Frankenberg‐Dinkel

2019

Environmental Microbiology

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Summary Organisms have evolved signal transduction systems to quickly adapt their lifestyle to internal and environmental changes. While protein kinases and two‐component systems are widely distributed in Bacteria, they are also found in Archaea but are less diversified and abundant. In this work, we analysed the function of the kinase RdmS and its role in a putative two‐component system in the methanogenic archaeon Methanosarcina acetivorans. RdmS is encoded upstream of the regulator MsrF, which activates the expression of the corrinoid/methyltransferase fusion protein MtsD. In contrast to a typical bacterial histidine kinase, RdmS lacks a membrane domain and the conserved histidine residue for phosphorylation, indicating a different mechanism of signal transduction in comparison to bacterial counterparts. RdmS covalently binds a heme cofactor and is thereby able to bind small molecules like CO and dimethyl sulfide. Interestingly, RdmS possesses a redox‐dependent autophosphorylation activity, which, however, is independent of the bound heme cofactor. In fact, our experimental data suggest a thiol‐based redox sensing mechanism by RdmS. Moreover, we were able to show that RdmS interacts with the regulator protein MsrF. From these data, we conclude RdmS to be a thiol‐based kinase sensing redox changes and forming an archaeal multicomponent system with the regulators MsrG/F/C.

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“…22 interactions are supported by at least one predicted linear motif interaction site. Automatic Kinase-specific Interaction Detection (AKID) method [36] exploits the sequence of the putative substrate, as well as the kinase specificity determinants to infer kinase-substrate interactions as phospho-sites. We combined the two approaches and taking sites with a stringent AKID score > 0.7 as additional specificity criteria for interaction prediction (Suppl.…”

Section: Kinase-substrate Interaction Motif Analysismentioning

confidence: 99%

Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins

Halwachs,

Moesslacher,

Kohlmayr

et al. 2023

Preprint

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The dysregulation of cellular signaling upon SARS-CoV-2 infection is mediated via direct protein interactions, with the human protein kinases constituting the major impact nodes in the signaling networks. Here, we employed a targeted yeast two-hybrid matrix approach to identify direct SARS-CoV-2 protein interactions with an extensive set of human kinases. We discovered 51 interactions involving 14 SARS-CoV-2 proteins and 29 human kinases, including many of the CAMK and CMGC kinase family members, as well as non-receptor tyrosine kinases. By integrating the interactions identified in our screen with transcriptomics and phospho-proteomics data, we revealed connections between SARS-CoV-2 protein interactions, kinase activity changes, and the cellular phospho-response to infection and identified altered activity patterns in infected cells for AURKB, CDK2, CDK4, CDK7, ABL2, PIM2, PLK1, NEK2, TRIB3, RIPK2, MAPK13, and MAPK14. Finally, we demonstrated direct inhibition of the FER human tyrosine kinase by the SARS-CoV-2 auxiliary protein ORF6, hinting at pressures underlying ORF6 changes observed in recent SARS-CoV-2 strains. Our study expands the SARS-CoV-2 – host interaction knowledge, illuminating the critical role of dysregulated kinase signaling during SARS-CoV-2 infection.

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Kinome-wide identification of phosphorylation networks in eukaryotic proteomes

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 12 publications

References 41 publications

Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources

Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources

Thiol‐based redox sensing in the methyltransferase associated sensor kinase RdmS in Methanosarcina acetivorans

Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins

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