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An Integrated Global Analysis of Compartmentalized HRAS Signaling.
Tapesh Santra1, Ana Herrero1, Javier Rodriguez1
1Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland.
Cell Reports
|March 14, 2019
Summary
This study introduces a framework integrating protein interaction, phosphoproteomics, and transcriptomics data. This approach reveals how spatially defined networks control HRAS signaling and gene transcription, uncovering distinct cellular functions.
Area of Science:
- Systems biology
- Molecular biology
- Cellular signaling
Background:
- Omics technologies provide global biological network data.
- Integrating diverse omics data for comprehensive interpretation is challenging.
Purpose of the Study:
- To present a conceptual framework for integrating protein interaction, phosphoproteomics, and transcriptomics data.
- To analyze HRAS signaling within different subcellular compartments using this integrated framework.
Main Methods:
- Developed a conceptual framework to integrate protein interaction, phosphoproteomics, and transcriptomics data.
- Applied the framework to analyze HRAS signaling from various subcellular locations.
Main Results:
- Spatially defined networks contribute specific functions to HRAS signaling.
- HRAS protein interactions at different sites differentially regulate kinase activation and gene transcription.
- HRAS signaling is strongest at the cell membrane but regulates the most genes from the endoplasmic reticulum.
- Distinct HRAS functions, including cell migration (ER) and cell survival (Golgi), were identified.
Conclusions:
- The integrated network provides a topologically and functionally resolved view of HRAS signaling.
- Spatially resolved HRAS signaling networks reveal distinct cellular functions and regulatory mechanisms.
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