In Silico Phosphoproteomic Profiling of the MAP3K3 Signaling Network.
- 1Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India.
- 2Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4II, UK.
- 3Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Abstract
Background
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is a serine/threonine kinase that exhibits oncogenic activity in various cancers. Despite the established role of MAP3K3 in signal transduction, its phosphosignaling landscape, including the mechanisms underlying its activation and the identification of its upstream kinases and downstream substrates, remains poorly characterized.Methods
To explore this network, we analyzed the global phosphoproteomics datasets to identify predominant sites of MAP3K3. Co-concordance and co-occurrence analyses were conducted to characterize the functional significance of site-specific phosphorylation of MAP3K3.Results
From the 588 profiling datasets and 124 differential datasets, we identified S340, S337, and S166 as predominant phosphosites. We then categorized the phosphosites in other proteins (PsOPs), which were positively and negatively co-concordant with the predominant sites of MAP3K3. From the known and predicted upstream kinases, substrates, and interactors, we isolated the PsOPs that have a role in carcinogenesis.Conclusions
Finally, by integrating these co-concordance data with the currently known and predicted upstream kinases, substrates, and interactors, we constructed a phosphosignaling network of MAP3K3-driven carcinogenesis. This network provides insights into the potential upstream kinases and substrates of MAP3K3 in the context of carcinogenesis.
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BibTeX
@article{john2026silico,
title = {{In Silico Phosphoproteomic Profiling of the MAP3K3 Signaling Network.}},
author = {Jetna John and Suhail Subair and Leona Dcunha and Althaf Mahin and Megha Madhusudhanan and Levin John and Athira Perunelly Gopalakrishnan and Mukhtar Ahmed and Rajesh Raju},
journal = {Proteomes},
year = {2026},
month = sep,
doi = {10.3390/proteomes14040050},
url = {https://europepmc.org/article/MED/42924748},
note = {CC BY},
}
RIS
TY - JOUR
TI - In Silico Phosphoproteomic Profiling of the MAP3K3 Signaling Network.
AU - Jetna John
AU - Suhail Subair
AU - Leona Dcunha
AU - Althaf Mahin
AU - Megha Madhusudhanan
AU - Levin John
AU - Athira Perunelly Gopalakrishnan
AU - Mukhtar Ahmed
AU - Rajesh Raju
PY - 2026
DA - 2026/09/28
JO - Proteomes
DO - 10.3390/proteomes14040050
UR - https://europepmc.org/article/MED/42924748
AB - Background Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is a serine/threonine kinase that exhibits oncogenic activity in various cancers. Despite the established role of MAP3K3 in signal transduction, its phosphosignaling landscape, including the mechanisms underlying its activation and the identification of its upstream kinases and downstream substrates, remains poorly characterized.Methods To explore this network, we analyzed the global phosphoproteomics datasets to identify predominant sites of MAP3K3. Co-concordance and co-occurrence analyses were conducted to characterize the functional significance of site-specific phosphorylation of MAP3K3.Results From the 588 profiling datasets and 124 differential datasets, we identified S340, S337, and S166 as predominant phosphosites. We then categorized the phosphosites in other proteins (PsOPs), which were positively and negatively co-concordant with the predominant sites of MAP3K3. From the known and predicted upstream kinases, substrates, and interactors, we isolated the PsOPs that have a role in carcinogenesis.Conclusions Finally, by integrating these co-concordance data with the currently known and predicted upstream kinases, substrates, and interactors, we constructed a phosphosignaling network of MAP3K3-driven carcinogenesis. This network provides insights into the potential upstream kinases and substrates of MAP3K3 in the context of carcinogenesis.
SN - 2227-7382
ER -