Lerner Research Institute Findings to be Published in Molecular Cell

Researchers in the Molecular Cardiology department of Cleveland Clinic’s Lerner Research Institute have discovered that a protein known to regulate heart failure and cancer tumors is not what scientists had thought it was.

The protein – known as integrin-linked kinase or ILK – was discovered in 1996. High levels of the protein were found in tumors and failing hearts, and it was widely regarded as a protein kinase in medical literature.

However, Lerner Research Institute’s Jun Qin, Ph.D., and research assistant Koichi Fukuda have discovered that ILK is not a protein kinase, but rather a pseudokinase.

“This finding will revolutionize the thinking of how ILK functions in cells,” said Dr. Qin. “We will see a significant rethinking of how ILK mediates various physiological and pathological processes. More importantly, this will lead to a completely new strategy to design drugs that target ILK for treating various ILK-mediated cancers and heart diseases.”

The study – “The Pseudoactive Site of ILK Is Essential for Its Binding to a-Parvin and Localization to Focal Adhesions” – will be published in the December 11 issue of  Molecular Cell.

Over the past decade, scientists and pharmaceutical companies have made extensive efforts to understand the mechanism of this protein and to develop ILK-based treatments for cancer and heart failure. Seeing ILK as a pseudokinase instead of a protein kinase offers a new target for drug development, because the new findings show that ILK acts as a hub to bind several important cellular targets as a network, which mechanically regulates the cell shape and cell movement.

Other researchers involved in the study were Sudhiranjan Gupta, Ph.D., at Lerner Research Institute, and Ka Chen and Chuanyue Wu at University of Pittsburgh.

The work was supported by the American Heart Association and National Institutes of Health.

About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. About 2,000 full-time salaried physicians and researchers and 7,600 nurses at Cleveland Clinic represent more than 100 medical specialties and subspecialties. In addition to its main campus, Cleveland Clinic operates nine regional hospitals in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas and Cleveland Clinic Canada. In 2008, there were more than 4.2 million visits throughout the Cleveland Clinic health system and 165,000 hospital admissions. Patients came for treatment from every state and from more than 80 countries. Visit Cleveland Clinic at clevelandclinic.org.

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