Yale Researcher Benjamin Turk: 'This online resource will be immensely valuable to the scientific community in advancing their research on cellular processes and disease mechanisms'

Researchers at Yale University recently analyzed more than 300 kinases in the human body that showed insights into what proteins the enzymes are most likely to target, which leads to a better understanding of human biology and treating diseases. According to a release on February 14 from Yale, the findings show how kinases recognize targets based on amino acid sequences, which provides a valuable online resource for other researchers.

"In most cases, we don't know which proteins specific kinases target, and this knowledge gap hinders our understanding of fundamental cellular processes and the development of potential treatments for diseases," said lead researcher Benjamin Turk, who is an associate professor of pharmacology at Yale School of Medicine.

According to the report, Yale researchers have made major strides in understanding the role of kinases in human biology and their potential implications for disease treatment. The researchers found crucial insights into the proteins the specialized enzymes are more likely to target. The findings were published in the prestigious scientific journal Nature, and offer valuable insights into signaling pathways and potential drug targets.

Kinases are a class of enzymes that are responsible for a process called phosphorylation. This is a vital regulatory mechanism in cellular signaling. When a cell senses a change in the environment, kinases play a vital role in initiating a chain reaction that ultimately alters the cell's function. Understanding the role of specific kinases and target proteins has been a challenging task for scientists due to the complexity and diversity of the enzymes.

Turk and his colleagues address the knowledge gap by investigating how the kinases recognize and interact target proteins. There was a focus on short sequences of amino acids surrounding phosphorylation sites, which are crucial for kinase recognition. By assembling various amino acid strings and measuring the speed of phosphorylation by different kinases, researchers were able to decipher which sequences were favored or not by specific kinases.

"We were able to establish a ranked list of possible options for researchers interested in knowing what their kinase of interest might phosphorylate or which kinase phosphorylates their protein of interest," Turk added. "This online resource will be immensely valuable to the scientific community in advancing their research on cellular processes and disease mechanisms." 

The researchers were particularly intrigued by an unexpected finding during the study. Some phosphorylation sites showed poor affinity for their known kinases but scored significantly worse for other kinases. Turk hypothesized that these phosphorylation sites may have evolved to evade the wrong kinases rather than to enhance recognition by the right kinases. 

These findings showed the intricacies of kinase specificity and how these critical enzymes can precisely regulate cellular processes. Turk and his colleagues delved deeper into the world of mitogen-activated protein kinases (MAP kinases). Despite molecular similarities, each MAP kinase plays a distinct role in the human body. Their second study, published in Science Signaling showed how different MAP kinases target proteins and their diverse effects.

Guangda Shi, the lead author of the second study and a former graduate student in Turk's lab now at the University of Pennsylvania, shared their discoveries

"Understanding how and where kinases act will help us gain insight into biological functions and how they go awry in diseases like cancer," She said.

Turk explained that some MAP kinases are often hyperactivated in cancer, and they have become attractive drug targets for cancer treatment. He said that by better understanding their signaling pathways, researchers can develop more targeted therapies for a large variety of diseases. He said this could revolutionize modern medicine.

The work done by the Yale researchers provides a major step forward in understanding kinases and their roles in cellular processes. With a comprehensive online resource at their disposal and a clearer grasp of kinase signaling pathways, researchers around the world are now poised to make strides in both fundamental biology and disease treatment. Due to this work and the discoveries from it, the potential for new and innovative treatments for various diseases has become more promising and could lead to a healthier and better understood future of medicine.

“Certain MAP kinases are frequently hyperactivated in cancer and they have become drug targets for treatment,” Turk explained. “Understanding how and where kinases act will help us understand their signaling pathways more deeply. And that will give us insight into all sorts of biological functions and where they go wrong in disease.”