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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors
1Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax, Tunisia.
Background:
Nuclear receptors (NRs) and Receptor tyrosine kinases (RTKs) are essential proteins in many cellular processes and sequence variations in their genes have been reported to be involved in many diseases including cancer. Although crosstalk between RTK and NR signalling and their contribution to the development of endocrine regulated cancers have been areas of intense investigation, the direct coupling of their signalling pathways remains elusive. In our understanding of the role and function of nuclear receptors on the cell membrane the interactions between nuclear receptors and tyrosine kinase receptors deserve further attention.
Results:
We constructed a human signalling network containing nuclear receptors and tyrosine kinase receptors that identified a network topology involving eleven highly connected hubs.We further developed an integrated knowledge database, denominated NR-RTK database dedicated to human RTKs and NRs and their vertebrate orthologs and their interactions. These interactions were inferred using computational tools and those supported by literature evidence are indicated. NR-RTK database contains links to other relevant resources and includes data on receptor ligands. It aims to provide a comprehensive interaction map that identifies complex dynamics and potential crosstalk involved.
Availability:
NR-RTK database is accessible at http://www.bioinfo-cbs.org/NR-RTK/ CONCLUSIONS: We infer that the NR-RTK interaction network is scale-free topology. We also uncovered the key receptors mediating the signal transduction between these two types of receptors. Furthermore, NR-RTK database is expected to be useful for researchers working on various aspects of the molecular basis of signal transduction by RTKs and NRs.
Insights
We mapped the signaling network of nuclear receptors (NRs) and receptor tyrosine kinases (RTKs), revealing key hubs and interactions. The NR-RTK database offers a comprehensive resource for studying crosstalk in diseases like cancer.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Systems biology
Background:
- Nuclear receptors (NRs) and receptor tyrosine kinases (RTKs) are crucial in cellular processes.
- Gene variations in NRs and RTKs are linked to diseases, including cancer.
- Direct coupling and crosstalk between NR and RTK signaling pathways are not fully understood, especially concerning cell membrane functions.
Purpose of the Study:
- To construct a human signaling network of NRs and RTKs.
- To develop an integrated knowledge database (NR-RTK database) for these receptors and their interactions.
- To identify key signaling hubs and potential crosstalk mechanisms.
Main Methods:
- Construction of a human signaling network integrating NRs and RTKs.
- Development of the NR-RTK database using computational inference and literature evidence.
- Analysis of network topology and identification of highly connected hubs.
Main Results:
- A human signaling network with eleven highly connected hubs was identified.
- The NR-RTK database was created, cataloging human NRs, RTKs, their vertebrate orthologs, and interactions.
- The interaction network exhibits a scale-free topology, and key signal-transducing receptors were uncovered.
Conclusions:
- The NR-RTK interaction network demonstrates a scale-free topology.
- Key receptors mediating signal transduction between NRs and RTKs have been identified.
- The NR-RTK database serves as a valuable resource for researchers investigating NR and RTK signaling.
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