by The Mount Sinai Hospital

KiNet functionalities. Credit: npj Systems Biology and Applications (2024). DOI: 10.1038/s41540-024-00442-5

Researchers from the Icahn School of Medicine at Mount Sinai have introduced KiNet, an interactive web portal designed to explore kinase-substrate interactions in human cellular systems. These interactions play a vital role in modulating complex signaling pathways that control various cellular processes, such as cell growth, differentiation, and response to environmental stimuli.

By integrating data from multiple public databases, KiNet enables the scientific community to visualize and study these interactions in systemwide contexts, enhancing the understanding of kinase functions and their implications in diseases like cancer, neurodegenerative disorders, and cardiovascular diseases.

Details of KiNet are published in npj Systems Biology and Applications.

Kinases are enzymes that modify other proteins by adding phosphate groups to them, a process known as phosphorylation. This modification regulates the activity, localization, and function of proteins, ultimately influencing various cellular activities. Disruption in these kinase-substrate interactions is often linked to diseases, making them major targets for therapeutic intervention.

Despite the abundance of data on kinases and their substrates, much of this information is scattered across multiple databases, making it challenging to interpret in the context of cellular systems. KiNet addresses this issue by aggregating data from major databases and providing a user-friendly platform for researchers to explore these interactions comprehensively.

"Kinases and their substrates are pivotal in cellular signaling pathways, and the ability to visualize these interactions in system-level contexts opens new avenues for understanding their roles in health and disease," said Gaurav Pandey, Ph.D., Professor of Genetics and Genomic Sciences at Icahn Mount Sinai and co-senior author of the paper. "KiNet not only aggregates existing data but also provides an interactive platform that will facilitate drug discovery and systems-level analysis."

KiNet's ability to visualize kinase-substrate interactions within pathways, domain families, and custom protein sets offers researchers a powerful tool for knowledge discovery. By focusing on system contexts, such as the network of interactions in signaling pathways, users can gain a more comprehensive view of how these important proteins operate. This capability holds promise for a wide range of applications, including drug discovery, where understanding the intricate relationships between kinases and substrates can reveal potential targets for therapeutic intervention.

In addition to its use in basic research, KiNet is poised to contribute to the development of new therapies. Many current drugs target kinases due to their central role in diseases such as cancer, where abnormal kinase activity drives tumor growth. KiNet's interactive approach to visualizing kinase interactions can assist researchers in identifying novel drug targets and understanding the effects of potential treatments on complex signaling pathways.

"KiNet represents a unique resource for the scientific community, bringing together diverse datasets and providing an accessible platform for visualizing kinase-substrate interactions," said Avner Schlessinger, Ph.D., Professor of Pharmacological Sciences at Icahn Mount Sinai and co-senior author of the paper. "We anticipate that KiNet will be a valuable tool in advancing both fundamental research and clinical applications, particularly in drug discovery and personalized medicine."

More information: John A. P. Sekar et al, A web portal for exploring kinase-substrate interactions, npj Systems Biology and Applications (2024). DOI: 10.1038/s41540-024-00442-5

Provided by The Mount Sinai Hospital