An Integrative Phosphoregulatory Landscape of FAK Signaling
4 affiliations
- 1Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India
- 2Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India
- 3Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
- 4Central Research Laboratory, Srinivas University, Mukka 574146, Karnataka, India
Abstract
Focal adhesion kinase (FAK) is a protein tyrosine kinase that plays a major role in regulating cell adhesion, proliferation, motility, and survival. While FAK-regulatory phosphosites play significant roles in cancer progression and metastasis, the broader perspective of its phosphorylation remains largely unknown. Therefore, mapping the phosphoregulatory networks provides significant insights into targeted therapies. To characterize the phosphorylations of FAK, we systematically retrieved PubMed-indexed studies and compiled large-scale cellular mass spectrometry-based phosphoproteomics datasets. An integrative, data-driven analysis was performed on 678 qualitative and 235 quantitative cellular phosphoproteomic datasets to map the signatures of FAK phosphorylation. The study observed that the S910 modification is the most frequently detected phosphorylation outside the catalytic kinase domain. This predicts a broader regulatory role of S910 in signaling than previously understood. Further, by integrating phosphosite co-detection patterns across diverse biological contexts, we characterized FAK phosphorylations and their co-regulated Phosphosites in Other Proteins (PsOPs). The phospho-coregulatory analysis of S910 and FAK activation phosphosites Y576, Y577, and Y861 provided distinct potential phosphosite cross-talks. Furthermore, the study predicts several potential candidate substrates and interactor PsOPs, providing a framework for prioritizing phosphosites for future experimental investigation. Moreover, the study also illustrated a hypothesized model of potential FAK phosphosite-specific coregulatory associations within gastrin-associated signaling. Taken together, these large-scale observations provide a data-driven foundation for future FAK-centered experimental approaches and understanding of its multifaceted role as a potential target.
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BibTeX
@article{george2026integrative,
title = {{An Integrative Phosphoregulatory Landscape of FAK Signaling}},
author = {Mejo George and Leona Dcunha and Mukhtar Ahmed and Althaf Mahin and Athira Perunelly Gopalakrishnan and Prashant Kumar Modi and Anoop Kumar G. Velikkakath and Rajesh Raju},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219484},
url = {https://www.mdpi.com/1422-0067/27/21/9484},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An Integrative Phosphoregulatory Landscape of FAK Signaling
AU - Mejo George
AU - Leona Dcunha
AU - Mukhtar Ahmed
AU - Althaf Mahin
AU - Athira Perunelly Gopalakrishnan
AU - Prashant Kumar Modi
AU - Anoop Kumar G. Velikkakath
AU - Rajesh Raju
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219484
UR - https://www.mdpi.com/1422-0067/27/21/9484
AB - Focal adhesion kinase (FAK) is a protein tyrosine kinase that plays a major role in regulating cell adhesion, proliferation, motility, and survival. While FAK-regulatory phosphosites play significant roles in cancer progression and metastasis, the broader perspective of its phosphorylation remains largely unknown. Therefore, mapping the phosphoregulatory networks provides significant insights into targeted therapies. To characterize the phosphorylations of FAK, we systematically retrieved PubMed-indexed studies and compiled large-scale cellular mass spectrometry-based phosphoproteomics datasets. An integrative, data-driven analysis was performed on 678 qualitative and 235 quantitative cellular phosphoproteomic datasets to map the signatures of FAK phosphorylation. The study observed that the S910 modification is the most frequently detected phosphorylation outside the catalytic kinase domain. This predicts a broader regulatory role of S910 in signaling than previously understood. Further, by integrating phosphosite co-detection patterns across diverse biological contexts, we characterized FAK phosphorylations and their co-regulated Phosphosites in Other Proteins (PsOPs). The phospho-coregulatory analysis of S910 and FAK activation phosphosites Y576, Y577, and Y861 provided distinct potential phosphosite cross-talks. Furthermore, the study predicts several potential candidate substrates and interactor PsOPs, providing a framework for prioritizing phosphosites for future experimental investigation. Moreover, the study also illustrated a hypothesized model of potential FAK phosphosite-specific coregulatory associations within gastrin-associated signaling. Taken together, these large-scale observations provide a data-driven foundation for future FAK-centered experimental approaches and understanding of its multifaceted role as a potential target.
SN - 1422-0067
ER -