Mount Sinai researchers introduce web portal empowering drug discovery and systems-level analysis of critical kinase-substrate interactions

New York City (Oct 3, 2024) - 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 were published in npj Systems Biology and Applications (DOI: 10.1038/s41540-024-00442-5).

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, PhD, 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 systems 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, PhD, 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."

For more information and to explore the KiNet portal, visit https://kinet.kinametrix.com.

The paper is titled “A web portal for exploring kinase-substrate interactions.”

This work was supported by National Institutes of Health grant U01CA271318.

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About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.  

Ranked 13th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 44 academic departments and 36 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases. 

Icahn Mount Sinai offers highly competitive MD, PhD, and Master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System. 

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public. 

Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs. 

Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others. 

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally. 

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai